BaP诱导H2AX磷酸化及其对细胞核蛋白表达的影响
|
摘要
多环芳烃(polycyclic aromatic hydrocarbons，PAHs)是广泛存在于水、沉积物、土壤、植物和空气环境中的污染物，主要来源于工业废气、汽车尾气、油烟、吸烟、熏制食品等。PAHs是极其稳定的，所以造成环境的持续污染。苯并芘(Benzo[a]pyrene，BaP)是典型的强致癌性的多环芳烃类化合物，对其已有许多深入的研究报道。BaP通过机体代谢产生的BPDE(benzo[a]pyrene-7，8-diol-9，10-epoxide)是目前已知的最强的致癌物之一。BaP可阻断细胞生长分化调节的信号转导，与DNA形成加合物，导致DNA的断裂，诱导p53基因突变等等。但是就BaP可否诱导细胞产生DNA双链断裂(double strandbreaks，DSBs)的标记γH2AX(磷酸化的组蛋白H2AX)，报道不一。而且关于BaP诱导γH2AX产生的周期依赖性及参与形成γH2AX的激酶的研究也未见报道。
此外，以往的研究结果仅在单方面揭示BaP可能的遗传毒性或致癌的机理。然而BaP诱导的遗传毒性与细胞应答，可能的致癌机理并不是由单一或几个基因造成的，癌变是多因素、多阶段的过程。单纯针对某一个基因开展工作，很难发现与癌症相关明确的机理。以基因组学和蛋白质组学为主的高通量扫描技术的出现为此研究提供了一种新的研究思路。通过分析一个生物过程中基因组或蛋白组的变化，可以全面地了解参与生物过程的相关基因，构建细胞应答网络，解析关键细胞信号转导通路，从而更深入地探讨其潜在的分子机制。应用此类技术，已对BaP所诱导的细胞应激反应进行了分析，并鉴定了一批应答基因和蛋白。但是作为一种主要以DNA为靶点的化合物，BaP诱导的DNA损伤，势必引起DNA修复应答，从而影响正常的基因表达，造成细胞内蛋白表达差异。因为参与DNA损伤应答的蛋白理论上都应在细胞核内，所以研究BaP对细胞核蛋白表达的影响可能会对理解其遗传毒性及癌变的机制提供更有效的信息。
鉴于以上原因，本研究首先系统地探讨了BaP处理细胞后对细胞生存率和细胞周期的影响，及其造成的DNA损伤是否可诱导γH2AX的产生。本论文的第一部分中，通过应用HeLa细胞我们首先验证BaP是否可诱导H2AX的磷酸化。采用MTT法，检测BaP对HeLa细胞生存率的影响；流式细胞技术分析了BaP对细胞周期的影响。采用了免疫荧光染色及Western-blot方法，研究了BaP诱导γH2AX的时间及浓度效应及γH2AX产生与细胞周期的关系。在此基础上，进一步使用基因缺失的细胞系及激酶抑制剂，研究了参与BaP诱H2AX磷酸化的激酶。
通过以上的研究发现，BaP只有在较高剂量和长时间处理情况下对细胞活力有影响；对细胞周期影响较明显，可使细胞滞留于S期。BaP在HeLa细胞中诱导γH2AX的产生，并具有显著的时间及浓度效应，且具有S期或G2／M期的依赖性。通过不同基因缺失细胞的研究发现，BaP同样也可诱导γH2AX的产生，而且PIKKs(phosphatidylinositol 3-kinase-like protein kinases)家族的主要成员，包括ATM(ataxia telangiectasia mutated kinase)、ATR(ATM and Rad3-related kinase)和DNA-PK(DNA-dependent protein kinase)，在功能上互补或重叠参与了这一过程。
本论文的第二部分主要应用蛋白组学的方法系统分析了BaP对HeLa细胞核蛋白表达的影响。研究中我们使用10μmol．L~(-1)的BaP处理HeLa细胞6 h、12 h、24 h后，提取核蛋白，进行Bradford定量。样本进行双向电泳分析，使用GS-800扫描仪获取图像。运用PDQuest 7.1软件分析数字化图像文件，发现差异表达的蛋白点；胶内酶解后使用液相色谱-串联质谱(LC-MS／MS)分析差异点。
结果发现，与对照组相比，BaP处理引起128个蛋白点表达发生了显著性的改变，对其中易切取的差异点进行了质谱分析，最终鉴定了24种理论上符合的蛋白。进一步对其中鉴定的Lamin A和Bub3蛋白进行了Western-blot，共聚焦显微镜(Confocal microscopy)验证，结果与双向电泳结果一致。在鉴定的蛋白中，发现了数种与RNA剪接相关的蛋白，提示BaP处理可能诱导变异剪接的产生。因此，进一步以Fas与CD44为靶基因，采用RT-PCR方法，检测其变异剪接体的变化，发现BaP引起Fas可溶性受体变异剪接体的表达改变。
以上研究为进一步了解BaP的遗传毒性及致癌机理提供了有益的信息，其中发现的DNA损伤应激反应中变异剪接现象值得更深入的研究。
Polycyclic aromatic hydrocarbons (PAHs) are wide-spread environmentalpollutants which have been detected in surface waters, sediments, soil, plants, and bothrural and urban air. Automobile exhaust, domestic wood burning and industrial wastebyproducts are all sources of PAHs. Without an external stimulus, PAHs are extremelystable, making them a persistent environmental problem. Benzo[a]pyrene (BaP) is arepresentative of carcinogenic PAHs, and has been under intensive studies. BaP ismetabolized into BPDE, one of the strongest carcinogens. BaP can block signaltransductions、cell growth and differentiation, form adducts with DNA, induce DNAbreaks, as well as cause mutation in p53 gene. However, there were conflicting reportsabout the ability of BaP to induceγH2AX (the phospohorylated form of histoneH2AX), a marker for DNA double strand breaks (DSBs). In addition, it is not clearBaP-inducedγH2AX is cell cycle dependent, and the kinases involved inγH2AXformation are not known.
In addition, previous studies usually only address one aspect of the possiblemechanisms for the carcinogenicity of BaP. However, it is clear that cancer is not theresult of a single or several genes, and carcinogenesis is a multi-factor, multi-stageprocess. Focusing on only a single gene is very difficult to elucidate the mechanismsfor cancer. The advent of high-throughput technologies, such as genomics andproteomics, provides a new angle for cancer study. By globally analyzing the changes of genes and proteins in a biological process, those involved can be identified,cellular response network can be constructed, key signal transduction pathway can beanalyzed, all of which could help understand the underlying molecular mechanism.Using such techniques, the cellular response to BaP treatment has been analyzed, and agroup of responsive genes/proteins has been identified. Nonetheless, as the maintarget for BaP is DNA, BaP-induced DNA damage would lead to DNA repair response,thus changes in gene expression, and eventually result in changes in protein expression.Since most of the DNA damage responsive proteins should reside in the nucleus, tostudy the effects of BaP on nuclear protein expression would provide betterinformation for the understanding of BaP-induced carcinogenesis.
Therefore, in this study, we first investigated the effects of BaP treatment on cellsurvival and cell cycle, and whether BaP-induced DNA damage can lead to thephosphorylation of H2AX. In the first part of this dissertation, by using HeLa cells,we examined the ability of BaP to induce H2AX phosphorylation. The effects of BaPon HeLa cell survival was measured by MTT assay; cell cycle was analyzed by flowcytometry. The time- and dose-response of BaP to induceγH2AX, as well as thecorrelation betweenγH2AX and cell cycle was evaluated by Western-blot andimmunofluorescent microscopy. Furthermore, using specific gene-deficient cells andkinase inhibitors, we analyzed the kinases involved in BaP-induced H2AXphosphorylation.
Our results showed that only at higher concentrations or longer incubation timesdid BaP affect cell survival. In contrast, BaP significantly affected cell cycle, causingarrest in the S and G2/M phase. BaP inducedγH2AX in a time- and dose-dependentmanner in HeLa cells, which also showed a cell cycle-dependent manner. BaP alsoinducedγH2AX in the different gene-deficient cell lines, and members of the PIKKsfamily, including ATM, ATR, and DNA-PK were involved in this process.
In the second part of this dissertation, we used proteomic method analyzed the effects of BaP on nuclear protein expression in HeLa cells. HeLa cells were treatedwith 10μmol.L~(-1) BaP for 6, 12, and 24 h. Nuclear protein was then extracted andprotein concentration was determined by Bradford method. After 2-dimensionalelectrophoresis, gel images were captured using a GS-800 scanner and analyzed byPDQuest 7.1 for differentially expressed protein spots. After in-gel digestion, proteinswere identified by liquid chromatography-tandem mass spectrometry.
It was found that compared to control, BaP treatment induced expression changesin over 128 proteins, and 24 were successfully identified by mass spectrometry. Twoof them, Lamin A and Bub 3, were further examined by Western blot and Confocalmicroscopy, and thus validated the 2-dimensional electrophoresis results. Among theidentified proteins, several are involved in alternative splicing, suggesting that BaPtreatment could induce alternative splicing. Therefore, we further examined changesin the splicing variants of two genes, Fas and CD44, using RT-PCR, and the resultsshowed that indeed BaP caused changes in the soluble splicing variant of Fas.
Taken together, results obtained from above study provided useful information forthe better understanding of the mechanisms for BaP-induced carcinogenesis, and thephenomenon of alternative splicing during DNA damage response is worth furtherstudy.
此外，以往的研究结果仅在单方面揭示BaP可能的遗传毒性或致癌的机理。然而BaP诱导的遗传毒性与细胞应答，可能的致癌机理并不是由单一或几个基因造成的，癌变是多因素、多阶段的过程。单纯针对某一个基因开展工作，很难发现与癌症相关明确的机理。以基因组学和蛋白质组学为主的高通量扫描技术的出现为此研究提供了一种新的研究思路。通过分析一个生物过程中基因组或蛋白组的变化，可以全面地了解参与生物过程的相关基因，构建细胞应答网络，解析关键细胞信号转导通路，从而更深入地探讨其潜在的分子机制。应用此类技术，已对BaP所诱导的细胞应激反应进行了分析，并鉴定了一批应答基因和蛋白。但是作为一种主要以DNA为靶点的化合物，BaP诱导的DNA损伤，势必引起DNA修复应答，从而影响正常的基因表达，造成细胞内蛋白表达差异。因为参与DNA损伤应答的蛋白理论上都应在细胞核内，所以研究BaP对细胞核蛋白表达的影响可能会对理解其遗传毒性及癌变的机制提供更有效的信息。
鉴于以上原因，本研究首先系统地探讨了BaP处理细胞后对细胞生存率和细胞周期的影响，及其造成的DNA损伤是否可诱导γH2AX的产生。本论文的第一部分中，通过应用HeLa细胞我们首先验证BaP是否可诱导H2AX的磷酸化。采用MTT法，检测BaP对HeLa细胞生存率的影响；流式细胞技术分析了BaP对细胞周期的影响。采用了免疫荧光染色及Western-blot方法，研究了BaP诱导γH2AX的时间及浓度效应及γH2AX产生与细胞周期的关系。在此基础上，进一步使用基因缺失的细胞系及激酶抑制剂，研究了参与BaP诱H2AX磷酸化的激酶。
通过以上的研究发现，BaP只有在较高剂量和长时间处理情况下对细胞活力有影响；对细胞周期影响较明显，可使细胞滞留于S期。BaP在HeLa细胞中诱导γH2AX的产生，并具有显著的时间及浓度效应，且具有S期或G2／M期的依赖性。通过不同基因缺失细胞的研究发现，BaP同样也可诱导γH2AX的产生，而且PIKKs(phosphatidylinositol 3-kinase-like protein kinases)家族的主要成员，包括ATM(ataxia telangiectasia mutated kinase)、ATR(ATM and Rad3-related kinase)和DNA-PK(DNA-dependent protein kinase)，在功能上互补或重叠参与了这一过程。
本论文的第二部分主要应用蛋白组学的方法系统分析了BaP对HeLa细胞核蛋白表达的影响。研究中我们使用10μmol．L~(-1)的BaP处理HeLa细胞6 h、12 h、24 h后，提取核蛋白，进行Bradford定量。样本进行双向电泳分析，使用GS-800扫描仪获取图像。运用PDQuest 7.1软件分析数字化图像文件，发现差异表达的蛋白点；胶内酶解后使用液相色谱-串联质谱(LC-MS／MS)分析差异点。
结果发现，与对照组相比，BaP处理引起128个蛋白点表达发生了显著性的改变，对其中易切取的差异点进行了质谱分析，最终鉴定了24种理论上符合的蛋白。进一步对其中鉴定的Lamin A和Bub3蛋白进行了Western-blot，共聚焦显微镜(Confocal microscopy)验证，结果与双向电泳结果一致。在鉴定的蛋白中，发现了数种与RNA剪接相关的蛋白，提示BaP处理可能诱导变异剪接的产生。因此，进一步以Fas与CD44为靶基因，采用RT-PCR方法，检测其变异剪接体的变化，发现BaP引起Fas可溶性受体变异剪接体的表达改变。
以上研究为进一步了解BaP的遗传毒性及致癌机理提供了有益的信息，其中发现的DNA损伤应激反应中变异剪接现象值得更深入的研究。
Polycyclic aromatic hydrocarbons (PAHs) are wide-spread environmentalpollutants which have been detected in surface waters, sediments, soil, plants, and bothrural and urban air. Automobile exhaust, domestic wood burning and industrial wastebyproducts are all sources of PAHs. Without an external stimulus, PAHs are extremelystable, making them a persistent environmental problem. Benzo[a]pyrene (BaP) is arepresentative of carcinogenic PAHs, and has been under intensive studies. BaP ismetabolized into BPDE, one of the strongest carcinogens. BaP can block signaltransductions、cell growth and differentiation, form adducts with DNA, induce DNAbreaks, as well as cause mutation in p53 gene. However, there were conflicting reportsabout the ability of BaP to induceγH2AX (the phospohorylated form of histoneH2AX), a marker for DNA double strand breaks (DSBs). In addition, it is not clearBaP-inducedγH2AX is cell cycle dependent, and the kinases involved inγH2AXformation are not known.
In addition, previous studies usually only address one aspect of the possiblemechanisms for the carcinogenicity of BaP. However, it is clear that cancer is not theresult of a single or several genes, and carcinogenesis is a multi-factor, multi-stageprocess. Focusing on only a single gene is very difficult to elucidate the mechanismsfor cancer. The advent of high-throughput technologies, such as genomics andproteomics, provides a new angle for cancer study. By globally analyzing the changes of genes and proteins in a biological process, those involved can be identified,cellular response network can be constructed, key signal transduction pathway can beanalyzed, all of which could help understand the underlying molecular mechanism.Using such techniques, the cellular response to BaP treatment has been analyzed, and agroup of responsive genes/proteins has been identified. Nonetheless, as the maintarget for BaP is DNA, BaP-induced DNA damage would lead to DNA repair response,thus changes in gene expression, and eventually result in changes in protein expression.Since most of the DNA damage responsive proteins should reside in the nucleus, tostudy the effects of BaP on nuclear protein expression would provide betterinformation for the understanding of BaP-induced carcinogenesis.
Therefore, in this study, we first investigated the effects of BaP treatment on cellsurvival and cell cycle, and whether BaP-induced DNA damage can lead to thephosphorylation of H2AX. In the first part of this dissertation, by using HeLa cells,we examined the ability of BaP to induce H2AX phosphorylation. The effects of BaPon HeLa cell survival was measured by MTT assay; cell cycle was analyzed by flowcytometry. The time- and dose-response of BaP to induceγH2AX, as well as thecorrelation betweenγH2AX and cell cycle was evaluated by Western-blot andimmunofluorescent microscopy. Furthermore, using specific gene-deficient cells andkinase inhibitors, we analyzed the kinases involved in BaP-induced H2AXphosphorylation.
Our results showed that only at higher concentrations or longer incubation timesdid BaP affect cell survival. In contrast, BaP significantly affected cell cycle, causingarrest in the S and G2/M phase. BaP inducedγH2AX in a time- and dose-dependentmanner in HeLa cells, which also showed a cell cycle-dependent manner. BaP alsoinducedγH2AX in the different gene-deficient cell lines, and members of the PIKKsfamily, including ATM, ATR, and DNA-PK were involved in this process.
In the second part of this dissertation, we used proteomic method analyzed the effects of BaP on nuclear protein expression in HeLa cells. HeLa cells were treatedwith 10μmol.L~(-1) BaP for 6, 12, and 24 h. Nuclear protein was then extracted andprotein concentration was determined by Bradford method. After 2-dimensionalelectrophoresis, gel images were captured using a GS-800 scanner and analyzed byPDQuest 7.1 for differentially expressed protein spots. After in-gel digestion, proteinswere identified by liquid chromatography-tandem mass spectrometry.
It was found that compared to control, BaP treatment induced expression changesin over 128 proteins, and 24 were successfully identified by mass spectrometry. Twoof them, Lamin A and Bub 3, were further examined by Western blot and Confocalmicroscopy, and thus validated the 2-dimensional electrophoresis results. Among theidentified proteins, several are involved in alternative splicing, suggesting that BaPtreatment could induce alternative splicing. Therefore, we further examined changesin the splicing variants of two genes, Fas and CD44, using RT-PCR, and the resultsshowed that indeed BaP caused changes in the soluble splicing variant of Fas.
Taken together, results obtained from above study provided useful information forthe better understanding of the mechanisms for BaP-induced carcinogenesis, and thephenomenon of alternative splicing during DNA damage response is worth furtherstudy.
引文
1. Tatsushi Toyookaa and Yuko Ibuki, a. (2007) Environmental Toxicology and Pharmacology 23, 256-263
2. Bostrom, C. E., Gerde, P., Hanberg, A., Jernstrom, B., Johansson, C., Kyrklund,
T., Rannug, A., Tornqvist, M., Victorin, K., and Westerholm, R. (2002) Environmental health perspectives 110 Suppl 3, 451-488
3. Toyooka, T., Ohnuki, G., and Ibuki, Y. (2008) Mutation research 650(2), 132-139
4. White, P. A., and Claxton, L. D. (2004) Mutation research 567(2-3), 227-345
5. NAKAGAWA Y(Hatano Res. Inst., K., Jpn) TAKIGAWA Y(Hatano Res. Inst., Kanagawa, Jpn) TANAKA N(Hatano Res. Inst., Kanagawa, Jpn) (2001) Environmental Mutagen Research Communications 23, 107-118
6. Dong, S., Fu, P. P., Shirsat, R. N., Hwang, H. M., Leszczynski, J., and Yu, H. (2002) Chemical research in toxicology 15(3), 400-407
7. Yu, H., Xia, Q., Yan, J., Herreno-Saenz, D., Wu, Y. S., Tang, I. W., and Fu, P. P. (2006) International journal of environmental research and public health 3(4), 348-354
8. Xue, W., and Warshawsky, D. (2005) Toxicology and applied pharmacology 206(1), 73-93
9. Gavrilov, B., Vezhenkova, I., Firsanov, D., Solovjeva, L., Svetlova, M., Mikhailov, V., and Tomilin, N. (2006) Biochemical and biophysical research communications 347(4), 1048-1052
10. Hung, H. S., Wu, W. J., Cheng, Y. W., Wu, T. C., Chang, K. L., and Lee, H. (2007) Mutation research 628(2), 107-116
11. Prise, K. M., Folkard, M., Kuosaite, V., Tartier, L., Zyuzikov, N., and Shao, C. (2006) Mutation research 597(1-2), 1-4
12. Toyooka, T., Ibuki, Y., Takabayashi, F., and Goto, R. (2006) Environmental and molecular mutagenesis 47(1), 38-47
13. Perera, F., Tang, D., Whyatt, R., Lederman, S. A., and Jedrychowski, W. (2005) Cancer Epidemiol Biomarkers Prey 14(3), 709-714
14. Ling, H., Sayer, J. M., Plosky, B. S., Yagi, H., Boudsocq, F., Woodgate, R., Jerina, D. M., and Yang, W. (2004) Proceedings of the National Academy of Sciences of the United States of America 101(8), 2265-2269
15. Arce, G. T., Allen, J. W., Doerr, C. L., Elmore, E., Hatch, G. G., Moore, M. M., Sharief, Y., Grunberger, D., and Nesnow, S. (1987) Cancer Res 47(13), 3388-3395
16. Jernstrom, B., and Graslund, A. (1994) Biophys Chem 49(3), 185-199
17. Sadikovic, B., and Rodenhiser, D. I. (2006) Toxicology and applied pharmacology 216(3), 458-468
18. Ferguson, L. R., and Philpott, M. (2008) Annu Rev Nutr 28, 313-329
19. Shrivastav, M., De Haro, L. P., and Nickoloff, J. A. (2008) Cell Res 18(1), 134-147
20. Downs, J. A. (2007) Oncogene 26(56), 7765-7772
21. Escargueil, A. E., Soares, D. G., Salvador, M., Larsen, A. K., and Henriques, J. A. (2008) Murat Res 658(3), 259-270
22. Kuo, L. J., and Yang, L. X. (2008) In Vivo 22(3), 305-309
23. Fernandez-Capetillo, O., Celeste, A., and Nussenzweig, A. (2003) Cell Cycle 2(5), 426-427
24. Cheng, W. H., Sakamoto, S., Fox, J. T., Komatsu, K., Carney, J., and Bohr, V. A. (2005) FEBS Lett 579(6), 1350-1356
25. Ward, I. M., Minn, K., Jorda, K. G., and Chen, J. (2003) The Journal of biological chemistry 278(22), 19579-19582
26. Gallmeier, E., Winter, J. M., Cunningham, S. C., Kahn, S. R., and Kern, S. E. (2005) Carcinogenesis 26(10), 1811-1820
27. Huang, X., and Darzynkiewicz, Z. (2006) Methods Mol Biol 314, 73-80
28. Yu, Y., Zhu, W., Diao, H., Zhou, C., Chen, F. F., and Yang, J. (2006) Toxicol In Vitro
29. Zhou, C., Li, Z., Diao, H., Yu, Y., Zhu, W., Dai, Y., Chen, F. F., and Yang, J. (2006) Mutat Res 604(1-2), 8-18
30. Burma, S., Chen, B. P., Murphy, M., Kurimasa, A., and Chen, D. J. (2001) The Journal of biological chemistry 276(45), 42462-42467
31. Wang, H., Wang, M., Wang, H., Bocker, W., and Iliakis, G. (2005) J Cell Physiol 202(2), 492-502
32. Koike, M., Mashino, M., Sugasawa, J., and Koike, A. (2008) J Radiat Res (Tokyo) 49(4), 445-449
33. Yukawa, M., Oda, S., Mitani, H., Nagata, M., and Aoki, F. (2007) Biochemical and biophysical research communications 358(2), 578-584
34. Stiff, T., O'Driscoll, M., Rief, N., Iwabuchi, K., Lobrich, M., and Jeggo, P. A. (2004) Cancer research 64(7), 2390-2396
35. Koike, M., Mashino, M., Sugasawa, J., and Koike, A. (2007) Biochemical and biophysical research communications 363(4), 1009-1012
36. Amrein, L., Loignon, M., Goulet, A. C., Dunn, M., Jean-Claude, B., Aloyz, R., and Panasci, L. (2007) The Journal of pharmacology and experimental therapeutics 321(3), 848-855
37. Toyooka, T., and Ibuki, Y. (2005) FEBS Lett 579(28), 6338-6342
38. Drukteinis, J. S., Medrano, T., Ablordeppey, E. A., Kitzman, J. M., and Shiverick, K. T. (2005) Placenta 26 Suppl A, S87-95
39. Yao, B., Fu, J., Hu, E., Qi, Y., and Zhou, Z. (2007) Toxicology 237(1-3), 210-217
40. Binkova, B., Giguere, Y., Rossner, P., Jr., Dostal, M., and Sram, R. J. (2000) Mutation research 471(1-2), 57-70
41. Nwagbara, O., Darling-Reed, S. F., Tucker, A., Harris, C., Abazinge, M., Thomas, R. D., and Gragg, R. D. (2007) International journal of environmental research and public health 4(1), 10-14
42. Ko, C. B., Kim, S. J., Park, C., Kim, B. R., Shin, C. H., Choi, S., Chung, S. Y., Noh, J. H., Jeun, J. H., Kim, N. S., and Park, R. (2004) Toxicology 199(1), 35-46
43. Daniel, R., Ramcharan, J., Rogakou, E., Taganov, K. D., Greger, J. G., Bonner, W., Nussenzweig, A., Katz, R. A., and Skalka, A. M. (2004) J Biol Chem 279(44), 45810-45814
44. Zhao, H., Tanaka, T., Halicka, H. D., Traganos, F., Zarebski, M., Dobrucki, J., and Darzynkiewicz, Z. (2007) Cytometry A 71(11), 905-914
45. Sekine-Suzuki, E., Yu, D., Kubota, N., Okayasu, R., and Anzai, K. (2008) Biochemical and biophysical research communications 377(2), 341-345
46. Ewald, B., Sampath, D., and Plunkett, W. (2007) Molecular cancer therapeutics 6(4), 1239-1248
47. Kato, T. A., Okayasu, R., and Bedford, J. S. (2008) Mutation research 639(1-2), 108-112
48. Ichijima, Y., Sakasai, R., Okita, N., Asahina, K., Mizutani, S., and Teraoka, H. (2005) Biochemical and biophysical research communications 336(3), 807-812
49. Mattsson, A., Jernstrom, B., Cotgreave, I. A., and Bajak, E. (2009) Chemico-biological interactions 177(1), 40-47
50. Mukherjee, B., Kessinger, C., Kobayashi, J., Chen, B. P., Chen, D. J., Chatterjee, A., and Burma, S. (2006) DNA repair 5(5), 575-590
51. Ye, M., Iu, B. C., Jia, X. W., Gao, A., Jiao, S., and Zhang, F. M. (2008) Zhonghua yu fang yi xue za zhi[Chinese journal of preventive medicine]42(6), 400-404
52. Tu, L. C., Matsui, S. I., and Beerman, T. A. (2005) Molecular cancer therapeutics 4(8), 1175-1185
53. Sarkaria, J. N., Tibbetts, R. S., Busby, E. C., Kennedy, A. P., Hill, D. E., and Abraham, R. T. (1998) Cancer research 58(19), 4375-4382
54. Sakasai, R., Shinohe, K., Ichijima, Y., Okita, N., Shibata, A., Asahina, K., and Teraoka, H. (2006) Genes Cells 11(3), 237-246
55. Cortez, D. (2003) The Journal of biological chemistry 278(39), 37139-37145
56. Filippova, M., Parkhurst, L., and Duerksen-Hughes, P. J. (2004) The Journal of biological chemistry 279(24), 25729-25744
57. Xu, Y., Ashley, T., Brainerd, E. E., Bronson, R. T., Meyn, M. S., and Baltimore, D. (1996) Genes & development 10(19), 2411-2422
58. Ai, R., Sandoval, A., Chen, D. J., Burma, S., and Labhart, P. (2004) 31(2), 91-96
59. Winter, H. K., Ehrlich, V. A., Grusch, M., Lackner, A., Schulte-Hermann, R., Grasl-Kraupp, B., Mikulits, W., and Knasmuller, S. (2008) Mutat Res 657(2), 133-139
60. Yang, J., and Duerksen-Hughes, P. (1998) Carcinogenesis 19(6), 1117-1125
61. Keogh, M. C., Kim, J. A., Downey, M., Fillingham, J., Chowdhury, D., Harrison, J. C., Onishi, M., Datta, N., Galicia, S., Emili, A., Lieberman, J., Shen, X., Buratowski, S., Haber, J. E., Durocher, D., Greenblatt, J. F., and Krogan, N. J. (2006) Nature 439(7075), 497-501
62. McManus, K. J., and Hendzel, M. J. (2005) Molecular biology of the cell 16(10), 5013-5025
63. Meng, L. H., Kohlhagen, G., Liao, Z. Y., Antony, S., Sausville, E., and Pommier, Y. (2005) Cancer research 65(12), 5337-5343
64. Petrini, J. H., and Stracker, T. H. (2003) Trends in cell biology 13(9), 458-462
65. Reitsema, T., Klokov, D., Banath, J. P., and Olive, P. L. (2005) DNA repair 4(10), 1172-1181
66. Tanaka, T., Halicka, H. D., Huang, X., Traganos, F., and Darzynkiewicz, Z. (2006) Cell cycle (Georgetown, Tex 5(17), 1940-1945
67. Mirzoeva, O. K., and Petrini, J. H. (2003) Mol Cancer Res 1(3), 207-218
68. Halicka, H. D., Huang, X., Traganos, F., King, M. A., Dai, W., and Darzynkiewicz, Z. (2005) Cell cycle (Georgetown, Tex 4(2), 339-345
69. Luo, Q., Yang, J., Zeng, Q. L., Zhu, X. M., Qian, Y. L., and Huang, H. F. (2006) Biology of reproduction 75(5), 673-680
70. Jackson, S. P. (2002) Carcinogenesis 23(5), 687-696
71. van Gent, D. C., Hoeijmakers, J. H., and Kanaar, R. (2001) Nat Rev Genet 2(3), 196-206
72. Blasina, A., Price, B. D., Turenne, G. A., and McGowan, C. H. (1999) Curr Biol 9(19), 1135-1138
73. Sarkaria, J. N., Busby, E. C., Tibbetts, R. S., Roos, P., Taya, Y., Karnitz, L. M., and Abraham, R. T. (1999) Cancer research 59(17), 4375-4382
74. O'Driscoll, M., Ruiz-Perez, V. L., Woods, C. G., Jeggo, P. A., and Goodship, J. A.
(2003) Nat Genet 33(4), 497-501
75. Yang, J., Yu, Y., Hamrick, H. E., and Duerksen-Hughes, P. J. (2003) Carcinogenesis 24(10), 1571-1580
76. Daniel, R., Marusich, E., Argyris, E., Zhao, R. Y., Skalka, A. M., and Pomerantz, R. J. (2005) J Virol 79(4), 2058-2065
77. Rowley, R., Martin, J. H., and Leeper, D. B. (1988) Radiation research 113(1), 58-70
78. Collis, S. J., DeWeese, T. L., Jeggo, P. A., and Parker, A. R. (2005) Oncogene 24(6), 949-961
79. Powis, G., Bonjouklian, R., Berggren, M. M., Gallegos, A., Abraham, R., Ashendel, C., Zalkow, L., Matter, W. F., Dodge, J., Grindey, G., and et al. (1994) Cancer research 54(9), 2419-2423
80. Yano, H., Nakanishi, S., Kimura, K., Hanai, N., Saitoh, Y., Fukui, Y., Nonomura, Y., and Matsuda, Y. (1993) The Journal of biological chemistry 268(34), 25846-25856
81. Rowley, R. (1992) Radiation research 129(2), 224-227
82. Nishijima, H., Nishitani, H., Saito, N., and Nishimoto, T. (2003) Genes Cells 8(5), 423-435
83. Wharton, W., and Goz, B. (1979) Biochem Pharmacol 28(6), 763-768
84. Wells, J. N., and Miller, J. R. (1988) Methods Enzymol 159, 489-496
85. Wang, H., Wang, X., Iliakis, G., and Wang, Y. (2003) Radiation research 159(3), 420-425
86. Wang, X., Wang, H., Iliakis, G., and Wang, Y. (2003) Radiation research 159(3), 426-432
87. Mirzayans, R., Severin, D., and Murray, D. (2006) Int J Radiat Oncol Biol Phys 66(5), 1498-1505
88. Kim, S. J., Ko, C. B., Park, C., Kim, B. R., Sung, T. H., Koh, D. H., Kim, N. S., Oh, K. J., Chung, S. Y., and Park, R. (2005) Archives of biochemistry and biophysics 444(2), 121-129
89. Matsuoka, S., Ballif, B. A., Smogorzewska, A., McDonald, E. R., 3rd, Hurov, K. E., Luo, J., Bakalarski, C. E., Zhao, Z., Solimini, N., Lerenthal, Y., Shiloh, Y., Gygi, S. P., and Elledge, S. J. (2007) Science (New York, N.Y 316(5828), 1160-1166
1. Tannheimer, S. L., Ethier, S. P., Caldwell, K. K., and Burchiel, S. W. (1998) Carcinogenesis 19(7), 1291-1297
2. Yoshii, S., Tanaka, M., Otsuki, Y., Fujiyama, T., Kataoka, H., Arai, H., Hanai, H., and Sugimura, H. (2001) Molecular and cellular biology 21(20), 6796-6807
3. Hussain, S. P., Amstad, P., Raja, K., Sawyer, M., Hofseth, L., Shields, P. G., Hewer, A., Phillips, D. H., Ryberg, D., Haugen, A., and Harris, C. C. (2001) Cancer research 61(17), 6350-6355
4. Kassie, F., Anderson, L. B., Higgins, L., Pan, Y., Matise, I., Negia, M., Upadhyaya, P., Wang, M., and Hecht, S. S. (2008) Carcinogenesis 29(3), 610-619
5. Olden, K., and Wilson, S. (2000) Nature reviews 1(2), 149-153
6. Peakall, D., and Shugart, L. (2002) Ecotoxicology (London, England) 11(1), 7
7. Akerman, G. S., Rosenzweig, B. A., Domon, O. E., McGarrity, L. J., Blankenship, L. R., Tsai, C. A., Culp, S. J., MacGregor, J. T., Sistare, F. D., Chen, J. J., and Morris, S. M. (2004) Mutation research 549(1-2), 43-64
8. Luo, W., Fan, W., Xie, H., Jing, L., Ricicki, E., Vouros, P., Zhao, L. P., and Zarbl, H. (2005) Chemical research in toxicology 15(4), 619-629
9．俞利荣，曾嵘，夏其昌．(1998) 生命的化学 18(6)，4-9
10. Patterson, S. D., and Aebersold, R. H. (2003) Nature genetics 33 Suppl, 311-323
11. O'Farrell, P. H. (1975) The Journal of biological chemistry 250(10), 4007-4021
12. Shen, W., Liu, H., and Yu, Y. (2007) Journal of proteome research 6(12), 4737-4748
13. Shen, W., Liu, H., and Yu, Y. (2008) Proteomics 8(17), 3450-3468
14. Gao, Z., Jin, J., Yang, J., and Yu, Y. (2004) Mutation research 550(1-2), 11-24
15. Yan, J. X., Wait, R., Berkelman, T., Harry, R. A., Westbrook, J. A., Wheeler, C. H., and Dunn, M. J. (2000) Electrophoresis 21(17), 3666-3672
16. Filippov, V., Schmidt, E. L., Filippova, M., and Duerksen-Hughes, P. J. (2008) Gene 420(1), 34-41
17. Hole, A. K., Belkhiri, A., Snell, L. S., and Watson, P. H. (1997) Breast cancer research and treatment 43(2), 165-173
18. Filippov, V., Filippova, M., and Duerksen-Hughes, P. J. (2007) Cancer research 67(16), 7621-7630
19. Sinclair, J., Weeks, M., Butt, A., Worthington, J. L., Akpan, A., Jones, N., Waterfield, M., Allanand, D., and Timms, J. F. (2006) Proteomics 6(17), 4755-4764
20. Taddei, A., Hediger, F., Neumann, F. R., and Gasser, S. M. (2004) Annual review of genetics 38, 305-345
21. Moir, R. D., Yoon, M., Khuon, S., and Goldman, R. D. (2000) The Journal of cell biology 151(6), 1155-1168
22. Belmont, A. S., Zhai, Y., and Thilenius, A. (1993) The Journal of cell biology 123(6 Pt 2),1671-1685
23. Stuurman, N., Heins, S., and Aebi, U. (1998) Journal of structural biology 122(1-2), 42-66
24. Rober, R. A., Weber, K., and Osbom, M. (1989) Development (Cambridge, England) 105(2),365-378
25. Rober, R. A., Gieseler, R. K., Peters, J. H., Weber, K., and Osbom, M. (1990) Experimental cell research 190(2), 185-194
26. Shumaker, D. K., Kuczmarski, E. R., and Goldman, R. D. (2003) Current opinion in cell biology 15(3), 358-366
27. Gruenbaum, Y., Goldman, R. D., Meyuhas, R., Mills, E., Margalit, A., Fridkin, A., Dayani, Y., Prokocimer, M., and Enosh, A. (2003) International review of cytology 226, 1-62
28. Gruenbaum, Y., Margalit, A., Goldman, R. D., Shumaker, D. K., and Wilson, K. L. (2005) Nature reviews 6(1), 21-31
29. Meier, J., Campbell, K. H., Ford, C. C., Stick, R., and Hutchison, C. J. (1991) Journal of cell science 98 ( Pt 3), 271-279
30. Sparta, T. P., Goldman, A. E., Wang, C., Huang, S., and Goldman, R. D. (2002) The Journal of cell biology 156(4), 603-608
31. Manju, K., Muralikrishna, B., and Pamaik, V. K. (2006) Journal of cell science 119(Pt 13), 2704-2714
32. Liu, B., Wang, J., Chan, K. M., Tjia, W. M., Deng, W., Guan, X., Huang, J. D., Li, K. M., Chau, P. Y., Chen, D. J., Pei, D., Pendas, A. M., Cadinanos, J., Lopez-Otin, C., Tse, H. F., Hutchison, C., Chen, J., Cao, Y., Cheah, K. S., Tryggvason, K., and Zhou, Z. (2005) Nature medicine 11(7), 780-785
33. Lees-Miller, S. P. (2006) DNA repair 5(2), 286-289
34. Grabsch, H., Takeno, S., Parsons, W. J., Pomjanski, N., Boecking, A., Gabbert, H. E., and Mueller, W. (2003) The Journal of pathology 200(1), 16-22
35. Fang, Y., Liu, T., Wang, X., Yang, Y. M., Deng, H., Kunicki, J., Traganos, F., Darzynkiewicz, Z., Lu, L., and Dai, W. (2006) Oncogene 25(25), 3598-3605
36. Sudakin, V., Chan, G. K., and Yen, T. J. (2001) The Journal of cell biology 154(5), 925-936
37. Diaz-Martinez, L. A., and Yu, H. (2007) Cell division 2, 23
38. Fang, G. (2002) Molecular biology of the cell 13(3), 755-766
39. Hardwick, K. G., Johnston, R. C., Smith, D. L., and Murray, A. W. (2000) The Journal of cell biology 145(5), 871-882
40. Greene, L. M., Campiani, G., Lawler, M., Williams, D. C., and Zisterer, D. M. (2008) Molecular pharmacology 73(2), 419-430
41. Zhang, S., Schlott, B., Gorlach, M., and Grosse, F. (2004) Nucleic acids research 32(1), 1-10
42. Lee, S. Y., Park, J. H., Kim, S., Park, E. J., Yun, Y., and Kwon, J. (2005) The Biochemical journal 388(Pt 1), 7-15
43. Moumen, A., Masterson, P., O'Connor, M. J., and Jackson, S. P. (2005) Cell 123(6), 1065-1078
44. Sheikh, M. S., Carrier, F., Papathanasiou, M. A., Hollander, M. C., Zhan, Q., Yu, K., and Fornace, A. J., Jr. (1997) The Journal of biological chemistry 272(42), 26720-26726
45. Yang, C., and Carrier, F. (2001) The Journal of biological chemistry 276(50), 47277-47284
46. Brand, M., Moggs, J. G., Oulad-Abdelghani, M., Lejeune, F., Dilworth, F. J., Stevenin, J., Almouzni, G., and Tora, L. (2001) The EMBO journal 20(12), 3187-3196
47. Matsuoka, S., Ballif, B. A., Smogorzewska, A., McDonald, E. R., 3rd, Hurov, K. E., Luo, J., Bakalarski, C. E., Zhao, Z., Solimini, N., Lerenthal, Y., Shiloh, Y., Gygi, S. P., and Elledge, S. J. (2007) Science (New York, N. Y316(5828), 1160-1166
48. Johnson, J. M., Castle, J., Garrett-Engele, P., Kan, Z., Loerch, P. M., Armour, C. D., Santos, R., Schadt, E. E., Stoughton, R., and Shoemaker, D. D. (2003) Science (New York, N. Y 302(5653), 2141-2144
49. Thorburn, A. (2004) Cellular signalling 16(2), 139-144
50. Hill, L. L., Ouhtit, A., Loughlin, S. M., Kripke, M. L., Ananthaswamy, H. N., and Owen-Schaub, L. B. (1999)Science (New York, N. Y 285(5429), 898-900
51. Mo, Y. Y., and Beck, W. T. (1999) Molecular pharmacology 55(2), 216-222
52. Chen, C., Chang, M. C., Hsieh, R. K., Chang, Y. F., Lin, J., and Tsan, K. W. (2005) Leukemia & lymphoma 46(12), 1785-1795
53. Li, C., Kato, M., Shiue, L., Shively, J. E., Ares, M., Jr., and Lin, R. J. (2006) Cancer research 66(4), 1990-1999
54. Wang, H., Guan, J., Wang, H., Perrault, A. R., Wang, Y., and Iliakis, G. (2001) Cancer research 61(23), 8554-8563
55. Din, S., Brill, S. J., Fairman, M. P., and Stillman, B. (1990) Genes & development 4(6), 968-977
56. Dutta, A., and Stillman, B. (1992) The EMBO journal 11(6), 2189-2199
57. Ogawa, K., Utsunomiya, T., Mimori, K., Tanaka, Y., Tanaka, F., Inoue, H., Murayama, S., and Mori, M. (2004) British journal of cancer 91(2), 282-286
58. Gartner, W., Rossbacher, J., Zierhut, B., Daneva, T., Base, W., Weissel, M., Waldhausl, W., Pastemack, M. S., and Wagner, L. (2003) Cell motility and the cytoskeleton 56(2), 79-93
59. Doyon, Y., Selleck, W., Lane, W. S., Tan, S., and Cote, J. (2004) Molecular and cellular biology 24(5), 1884-1896
60. Cowling, V. H., and Cole, M. D. (2006) Seminars in cancer biology 16(4), 242-252
61. Wang, X., Chen, C. F., Baker, P. R., Chen, P. L., Kaiser, P., and Huang, L. (2007) Biochemistry 46(11), 3553-3565
62. Roessler, M., Rollinger, W., Mantovani-Endl, L., Hagmann, M. L., Palme, S., Berndt, P., Engel, A. M., Pfeffer, M., Karl, J., Bodenmuller, H., Ruschoff, J., Henkel, T., Rohr, G., Rossol, S., Rosch, W., Langen, H., Zolg, W., and Tacke, M. (2006)Mol Cell Proteomics 5(11), 2092-2101
63. Hall, P. A., Jung, K., Hillan, K. J., and Russell, S. E. (2005) The Journal of pathology 206(3), 269-278
64. Montagna, C., Lyu, M. S., Hunter, K., Lukes, L., Lowther, W., Reppert, T., Hissong, B., Weaver, Z., and Ried, T. (2003) Cancer research 63(9), 2179-2187
1. Harper, J. W., and Elledge, S. J. (2007) Molecular cell 28(5), 739-745
2. Petrini, J. H., and Stracker, T. H. (2003) Trends in cell biology 13(9), 458-462
3. Lukas, C., Falck, J., Bartkova, J., Bartek, J., and Lukas, J. (2003) Nature cell biology 5(3), 255-260
4. Zhou, B. B., and Elledge, S. J. (2000) Nature 408(6811), 433-439
5. Mirzoeva, O. K., and Petrini, J. H. (2001) Molecular and cellular biology 21(1), 281-288
6. Paull, T. T., Rogakou, E. P., Yamazaki, V., Kirchgessner, C. U., Gellert, M., and Bonner, W. M. (2000) Curr Biol 10(15), 886-895
7. Rogakou, E. P., Boon, C., Redon, C., and Bonner, W. M. (1999) The Journal of cell biology 146(5), 905-916
8. Mirzoeva, O. K., and Petrini, J. H. (2003) Mol Cancer Res 1(3), 207-218
9. Fernandez-Capetillo, O., Mahadevaiah, S. K., Celeste, A., Romanienko, P. J., Camerini-Otero, R. D., Bonner, W. M., Manova, K., Burgoyne, P., and Nussenzweig, A. (2003) Developmental cell 4(4), 497-508
10. Lou, Z., Minter-Dykhouse, K., Wu, X., and Chen, J. (2003) Nature 421(6926), 957-961
11. Xu, X., and Stern, D. F. (2003) The Journal of biological chemistry 278(10), 8795-8803
12. Goldberg, M., Stucki, M., Falck, J., D'Amours, D., Rahman, D., Pappin, D., Bartek, J., and Jackson, S. P. (2003)Nature 421 (6926), 952-956
13. Burma, S., Chen, B. P., Murphy, M., Kurimasa, A., and Chen, D. J. (2001) The Journal of biological chemistry 276(45), 42462-42467
14. Stewart, G. S., Wang, B., Bignell, C. R., Taylor, A. M., and Elledge, S. J. (2003) Nature 421 (6926), 961-966
15. Downs, J. A. (2007) Oncogene 26(56), 7765-7772
16. van Attikum, H., and Gasser, S. M. (2005) Nature reviews 6(10), 757-765
17. Costelloe, T., Fitzgerald, J., Murphy, N. J., Flaus, A., and Lowndes, N. F. (2006) Experimental cell research 312(14), 2677-2686
18. Alami, R., Fan, Y., Pack, S., Sonbuchner, T. M., Besse, A., Lin, Q., Greally, J. M., Skoultchi, A. I., and Bouhassira, E. E. (2003) Proceedings of the National Academy of Sciences of the United States of America 100(10), 5920-5925
19. Fan, Y., Nikitina, T., Zhao, J., Fleury, T. J., Bhattacharyya, R., Bouhassira, E. E., Stein, A., Woodcock, C. L., and Skoultchi, A. I. (2005) Cell 123(7), 1199-1212
20. Konishi, A., Shimizu, S., Hirota, J., Takao, T., Fan, Y., Matsuoka, Y., Zhang, L., Yoneda, Y., Fujii, Y., Skoultchi, A. I., and Tsujimoto, Y. (2003) Cell 114(6), 673-688
21. Funayama, R., Saito, M., Tanobe, H., and Ishikawa, F. (2006) The Journal of cell biology 175(6), 869-880
22. Campisi, J. (2005) Science (New York, N.Y 309(5736), 886-887
23. Reeves, R., and Adair, J. E. (2005) DNA repair 4(8), 926-938
24. Travers, A. A. (2003) EMBO reports 4(2), 131-136
25. Yamanaka, S., Katayama, E., Yoshioka, K., Nagaki, S., Yoshida, M., and Teraoka, H. (2002) Biochemical and biophysical research communications 292(1), 268-273
26. Celeste, A., Petersen, S., Romanienko, P. J., Fernandez-Capetillo, O., Chen, H. T., Sedelnikova, O. A., Reina-San-Martin, B., Coppola, V., Meffre, E., Difilippantonio, M. J., Redon, C., Pilch, D. R., Olaru, A., Eckhaus, M., Camerini-Otero, R. D., Tessarollo, L., Livak, F., Manova, K., Bonner, W. M., Nussenzweig, M. C., and Nussenzweig, A. (2002) Science (New York, N. Y 296(5569), 922-927
27. Jha, S., Shibata, E., and Dutta, A. (2008) Molecular and cellular biology 28(8), 2690-2700
28. Celeste, A., Fernandez-Capetillo, O., Kruhlak, M. J., Pilch, D. R., Staudt, D. W., Lee, A., Bonner, R. F., Bonner, W. M., and Nussenzweig, A. (2003) Nature cell biology 5(7), 675-679
29. Shroff, R., Arbel-Eden, A., Pilch, D., Ira, G., Bonner, W. M., Petrini, J. H., Haber, J. E., and Lichten, M. (2004) Curr Biol 14(19), 1703-1711
30. Lukas, C., Melander, F., Stucki, M., Falck, J., Bekker-Jensen, S., Goldberg, M., Lerenthal, Y., Jackson, S. P., Bartek, J., and Lukas, J. (2004) The EMBO journal 23(13), 2674-2683
31. Downs, J. A., Allard, S., Jobin-Robitaille, O., Javaheri, A., Auger, A., Bouchard, N., Kron, S. J., Jackson, S. P., and Cote, J. (2004) Molecular cell 16(6), 979-990
32. Soutoglou, E., and Misteli, T. (2008) Science (New York, N.Y 320(5882), 1507-1510
33. Bonilla, C. Y., Melo, J. A., and Toezyski, D. P. (2008) Molecular cell 30(3), 267-276
34. Wood, J. L., and Chen, J. (2008) Trends in cell biology 18(10), 451-455
1. Tatsushi Toyookaa and Yuko Ibuki, a. (2007) Environmental Toxicology and Pharmacology 23, 256-263
2. Bostrom, C. E., Gerde, P., Hanberg, A., Jernstrom, B., Johansson, C., Kyrklund, T., Rarmug, A., Tornqvist, M., Victorin, K., and Westerholm, R. (2002) Environmental health perspectives 110 Suppl 3, 451-488
3. Toyooka, T., Ohnuki, G., and Ibuki, Y. (2008) Mutation research 650(2), 132-139
4. White, P. A., and Claxton, L. D. (2004) Mutation research 567(2-3), 227-345
5. Xue, W., and Warshawsky, D. (2005) Toxicology and applied pharmacology 206(1), 73-93
6. NAKAGAWA Y(Hatano Res. Inst., K., Jpn) TAKIGAWA Y(Hatano Res. Inst., Kanagawa, Jpn) TANAKA N(Hatano Res. Inst., Kanagawa, Jpn) (2001) Environmental Mutagen Research Communications 23, 107-118
7. Dong, S., Fu, P. P., Shirsat, R. N., Hwang, H. M., Leszczynski, J., and Yu, H. (2002) Chemical research in toxicology 15(3), 400-407
8. tatsushi toyooka, y. i. (2007) enviornmental toxicology and pharmacology 23, 256-263
9. Yang, S. K. (1988) Biochemical pharmacology 37(1), 61-70
10. Levin, W., Buening, M. K., Wood, A. W., Chang, R. L., Kedzierski, B., Thakker, D. R., Boyd, D. R., Gadaginamath, G. S., Armstrong, R. N., Yagi, H., Karle, J. M., Slaga, T. J., Jerina, D. M., and Conney, A. H. (1980) The Journal of biological chemistry 255(19), 9067-9074
11. thakker, D. R., Yagi,H., levin,W.,. (1985) bioactivation of foreign compounds, academic press, new york, 177-242
12. ragan, E. G., Cavalieri,E.L., Tibbel,S.R.,. (1988) J. Am. Chem. Soc. 110, 4023-4029
13. Cavalieri, E. L., and Rogan, E. G. (1992) Pharmacology & therapeutics 55(2), 183-199
14. Xue, W., Zapien, D., and Warshawsky, D. (1999) Chemical research in toxicology 12(12), 1234-1239
15. Penning, T. M., Ohnishi, S. T., Ohnishi, T., and Harvey, R. G. (1996) Chemical research in toxicology 9(1), 84-92
16. Chung, H. S., Harvey, R. G., Armstrong, R. N., and Jarabak, J. (1987) The Journal of biological chemistry 262(26), 12448-12451
17. McCoull, K. D., Rindgen, D., Blair, I. A., and Penning, T. M. (1999) Chemical research in toxicology 12(3), 237-246
18. Penning, T. M., Burczynski, M. E., Hung, C. F., McCoull, K. D., Palackal, N. T., and Tsuruda, L. S. (1999) Chemical research in toxicology 12(1), 1-18
19. dipple, A. (1994), 107-129
20. Wolfe, A. R., Smith, T. J., and Meehan, T. (2004) Chemical research in toxicology 17(4), 476-491
21. Klinedinst, D. K., and Drinkwater, N. R. (1992) Molecular carcinogenesis 6(1), 32-42
22. Schaaper, R. M., Kunkel, T. A., and Loeb, L. A. (1983) Proceedings of the National Academy of Sciences of the United States of America 80(2), 487-491
23. Shou, M., Harvey, R. G., and Penning, T. M. (1993) Carcinogenesis 14(3), 475-482
24. Balu, N., Padgett, W. T., Lambert, G. R., Swank, A. E., Richard, A. M., and Nesnow, S. (2004) Chemical research in toxicology 17(6), 827-838
25. Beckman, K. B., and Ames, B. N. (1997) The Journal of biological chemistry 272(32), 19633-19636
26. Yu, H. (2002) Journal of environmental science and health 20(2), 149-183
27. Yu, H., Xia, Q., Yan, J., Herreno-Saenz, D., Wu, Y. S., Tang, I. W., and Fu, P. P. (2006) International journal of environmental research and public health 3(4), 348-354
28. RC Swartz, S. F., JO Lamberson, FA Cole. (1997) Environmental Toxicology and Chemistry 16, 2151-2157
29. Gao, D., Luo, Y., Guevara, D., Wang, Y., Rui, M., Goldwyn, B., Lu, Y., Smith, E. C., Lebwohl, M., and Wei, H. (2005) Free radical biology & medicine 39(9), 1177-1183
30. Gavrilov, B., Vezhenkova, I., Firsanov, D., Solovjeva, L., Svetlova, M., Mikhailov, V., and Tomilin, N. (2006) Biochemical and biophysical research communications 347(4), 1048-1052
31. Hung, H. S., Wu, W. J., Cheng, Y. W., Wu, T. C., Chang, K. L., and Lee, H. (2007) Mutation research 628(2), 107-116
32. Prise, K. M., Folkard, M., Kuosaite, V., Tartier, L., Zyuzikov, N., and Shao, C. (2006) Mutation research 597(1-2), 1-4
33. Dong, S., Hwang, H. M., Harrison, C., Holloway, L., Shi, X., and Yu, H. (2000) Bulletin of environmental contamination and toxicology 64(4), 467-474
34. Strniste, G. F., Martinez, E., Martinez, A. M., and Brake, R. J. (1980) Cancer research 40(2), 245-252
35. Utsumi, H., Kitani, H., Chang-Liu, C. M., and Elkind, M. M. (1987) Carcinogenesis 8(10), 1439-1444
36. Tuveson, R. W., Wang, G. R., Wang, T. P., and Kagan, J. (1990) Photochemistry and photobiology 52(5), 993-1002
37. Toyooka, T., Ibuki, Y., Takabayashi, F., and Goto, R. (2006) Environmental and molecular mutagenesis 47(1), 38-47
38. Toyooka, T., Ibuki, Y., Koike, M., Ohashi, N., Takahashi, S., and Goto, R. (2004) Biochemical and biophysical research communications 322(2), 631-636
39. Wang, L., Yan, J., Wang, S., Cohly, H., Fu, P. P., Hwang, H. M., and Yu, H. (2004) Mutation research 562(1-2), 143-150
40. Zhang, X., Wu, R. S., Fu, W., Xu, L., and Lain, P. K. (2004) Chemosphere 55(10), 1303-1308
41. Liu, Z., Lu, Y., Rosenstein, B., Lebwohl, M., and Wei, H. (1998) Biochemistry 37(28), 10307-10312
2. Bostrom, C. E., Gerde, P., Hanberg, A., Jernstrom, B., Johansson, C., Kyrklund,
T., Rannug, A., Tornqvist, M., Victorin, K., and Westerholm, R. (2002) Environmental health perspectives 110 Suppl 3, 451-488
3. Toyooka, T., Ohnuki, G., and Ibuki, Y. (2008) Mutation research 650(2), 132-139
4. White, P. A., and Claxton, L. D. (2004) Mutation research 567(2-3), 227-345
5. NAKAGAWA Y(Hatano Res. Inst., K., Jpn) TAKIGAWA Y(Hatano Res. Inst., Kanagawa, Jpn) TANAKA N(Hatano Res. Inst., Kanagawa, Jpn) (2001) Environmental Mutagen Research Communications 23, 107-118
6. Dong, S., Fu, P. P., Shirsat, R. N., Hwang, H. M., Leszczynski, J., and Yu, H. (2002) Chemical research in toxicology 15(3), 400-407
7. Yu, H., Xia, Q., Yan, J., Herreno-Saenz, D., Wu, Y. S., Tang, I. W., and Fu, P. P. (2006) International journal of environmental research and public health 3(4), 348-354
8. Xue, W., and Warshawsky, D. (2005) Toxicology and applied pharmacology 206(1), 73-93
9. Gavrilov, B., Vezhenkova, I., Firsanov, D., Solovjeva, L., Svetlova, M., Mikhailov, V., and Tomilin, N. (2006) Biochemical and biophysical research communications 347(4), 1048-1052
10. Hung, H. S., Wu, W. J., Cheng, Y. W., Wu, T. C., Chang, K. L., and Lee, H. (2007) Mutation research 628(2), 107-116
11. Prise, K. M., Folkard, M., Kuosaite, V., Tartier, L., Zyuzikov, N., and Shao, C. (2006) Mutation research 597(1-2), 1-4
12. Toyooka, T., Ibuki, Y., Takabayashi, F., and Goto, R. (2006) Environmental and molecular mutagenesis 47(1), 38-47
13. Perera, F., Tang, D., Whyatt, R., Lederman, S. A., and Jedrychowski, W. (2005) Cancer Epidemiol Biomarkers Prey 14(3), 709-714
14. Ling, H., Sayer, J. M., Plosky, B. S., Yagi, H., Boudsocq, F., Woodgate, R., Jerina, D. M., and Yang, W. (2004) Proceedings of the National Academy of Sciences of the United States of America 101(8), 2265-2269
15. Arce, G. T., Allen, J. W., Doerr, C. L., Elmore, E., Hatch, G. G., Moore, M. M., Sharief, Y., Grunberger, D., and Nesnow, S. (1987) Cancer Res 47(13), 3388-3395
16. Jernstrom, B., and Graslund, A. (1994) Biophys Chem 49(3), 185-199
17. Sadikovic, B., and Rodenhiser, D. I. (2006) Toxicology and applied pharmacology 216(3), 458-468
18. Ferguson, L. R., and Philpott, M. (2008) Annu Rev Nutr 28, 313-329
19. Shrivastav, M., De Haro, L. P., and Nickoloff, J. A. (2008) Cell Res 18(1), 134-147
20. Downs, J. A. (2007) Oncogene 26(56), 7765-7772
21. Escargueil, A. E., Soares, D. G., Salvador, M., Larsen, A. K., and Henriques, J. A. (2008) Murat Res 658(3), 259-270
22. Kuo, L. J., and Yang, L. X. (2008) In Vivo 22(3), 305-309
23. Fernandez-Capetillo, O., Celeste, A., and Nussenzweig, A. (2003) Cell Cycle 2(5), 426-427
24. Cheng, W. H., Sakamoto, S., Fox, J. T., Komatsu, K., Carney, J., and Bohr, V. A. (2005) FEBS Lett 579(6), 1350-1356
25. Ward, I. M., Minn, K., Jorda, K. G., and Chen, J. (2003) The Journal of biological chemistry 278(22), 19579-19582
26. Gallmeier, E., Winter, J. M., Cunningham, S. C., Kahn, S. R., and Kern, S. E. (2005) Carcinogenesis 26(10), 1811-1820
27. Huang, X., and Darzynkiewicz, Z. (2006) Methods Mol Biol 314, 73-80
28. Yu, Y., Zhu, W., Diao, H., Zhou, C., Chen, F. F., and Yang, J. (2006) Toxicol In Vitro
29. Zhou, C., Li, Z., Diao, H., Yu, Y., Zhu, W., Dai, Y., Chen, F. F., and Yang, J. (2006) Mutat Res 604(1-2), 8-18
30. Burma, S., Chen, B. P., Murphy, M., Kurimasa, A., and Chen, D. J. (2001) The Journal of biological chemistry 276(45), 42462-42467
31. Wang, H., Wang, M., Wang, H., Bocker, W., and Iliakis, G. (2005) J Cell Physiol 202(2), 492-502
32. Koike, M., Mashino, M., Sugasawa, J., and Koike, A. (2008) J Radiat Res (Tokyo) 49(4), 445-449
33. Yukawa, M., Oda, S., Mitani, H., Nagata, M., and Aoki, F. (2007) Biochemical and biophysical research communications 358(2), 578-584
34. Stiff, T., O'Driscoll, M., Rief, N., Iwabuchi, K., Lobrich, M., and Jeggo, P. A. (2004) Cancer research 64(7), 2390-2396
35. Koike, M., Mashino, M., Sugasawa, J., and Koike, A. (2007) Biochemical and biophysical research communications 363(4), 1009-1012
36. Amrein, L., Loignon, M., Goulet, A. C., Dunn, M., Jean-Claude, B., Aloyz, R., and Panasci, L. (2007) The Journal of pharmacology and experimental therapeutics 321(3), 848-855
37. Toyooka, T., and Ibuki, Y. (2005) FEBS Lett 579(28), 6338-6342
38. Drukteinis, J. S., Medrano, T., Ablordeppey, E. A., Kitzman, J. M., and Shiverick, K. T. (2005) Placenta 26 Suppl A, S87-95
39. Yao, B., Fu, J., Hu, E., Qi, Y., and Zhou, Z. (2007) Toxicology 237(1-3), 210-217
40. Binkova, B., Giguere, Y., Rossner, P., Jr., Dostal, M., and Sram, R. J. (2000) Mutation research 471(1-2), 57-70
41. Nwagbara, O., Darling-Reed, S. F., Tucker, A., Harris, C., Abazinge, M., Thomas, R. D., and Gragg, R. D. (2007) International journal of environmental research and public health 4(1), 10-14
42. Ko, C. B., Kim, S. J., Park, C., Kim, B. R., Shin, C. H., Choi, S., Chung, S. Y., Noh, J. H., Jeun, J. H., Kim, N. S., and Park, R. (2004) Toxicology 199(1), 35-46
43. Daniel, R., Ramcharan, J., Rogakou, E., Taganov, K. D., Greger, J. G., Bonner, W., Nussenzweig, A., Katz, R. A., and Skalka, A. M. (2004) J Biol Chem 279(44), 45810-45814
44. Zhao, H., Tanaka, T., Halicka, H. D., Traganos, F., Zarebski, M., Dobrucki, J., and Darzynkiewicz, Z. (2007) Cytometry A 71(11), 905-914
45. Sekine-Suzuki, E., Yu, D., Kubota, N., Okayasu, R., and Anzai, K. (2008) Biochemical and biophysical research communications 377(2), 341-345
46. Ewald, B., Sampath, D., and Plunkett, W. (2007) Molecular cancer therapeutics 6(4), 1239-1248
47. Kato, T. A., Okayasu, R., and Bedford, J. S. (2008) Mutation research 639(1-2), 108-112
48. Ichijima, Y., Sakasai, R., Okita, N., Asahina, K., Mizutani, S., and Teraoka, H. (2005) Biochemical and biophysical research communications 336(3), 807-812
49. Mattsson, A., Jernstrom, B., Cotgreave, I. A., and Bajak, E. (2009) Chemico-biological interactions 177(1), 40-47
50. Mukherjee, B., Kessinger, C., Kobayashi, J., Chen, B. P., Chen, D. J., Chatterjee, A., and Burma, S. (2006) DNA repair 5(5), 575-590
51. Ye, M., Iu, B. C., Jia, X. W., Gao, A., Jiao, S., and Zhang, F. M. (2008) Zhonghua yu fang yi xue za zhi[Chinese journal of preventive medicine]42(6), 400-404
52. Tu, L. C., Matsui, S. I., and Beerman, T. A. (2005) Molecular cancer therapeutics 4(8), 1175-1185
53. Sarkaria, J. N., Tibbetts, R. S., Busby, E. C., Kennedy, A. P., Hill, D. E., and Abraham, R. T. (1998) Cancer research 58(19), 4375-4382
54. Sakasai, R., Shinohe, K., Ichijima, Y., Okita, N., Shibata, A., Asahina, K., and Teraoka, H. (2006) Genes Cells 11(3), 237-246
55. Cortez, D. (2003) The Journal of biological chemistry 278(39), 37139-37145
56. Filippova, M., Parkhurst, L., and Duerksen-Hughes, P. J. (2004) The Journal of biological chemistry 279(24), 25729-25744
57. Xu, Y., Ashley, T., Brainerd, E. E., Bronson, R. T., Meyn, M. S., and Baltimore, D. (1996) Genes & development 10(19), 2411-2422
58. Ai, R., Sandoval, A., Chen, D. J., Burma, S., and Labhart, P. (2004) 31(2), 91-96
59. Winter, H. K., Ehrlich, V. A., Grusch, M., Lackner, A., Schulte-Hermann, R., Grasl-Kraupp, B., Mikulits, W., and Knasmuller, S. (2008) Mutat Res 657(2), 133-139
60. Yang, J., and Duerksen-Hughes, P. (1998) Carcinogenesis 19(6), 1117-1125
61. Keogh, M. C., Kim, J. A., Downey, M., Fillingham, J., Chowdhury, D., Harrison, J. C., Onishi, M., Datta, N., Galicia, S., Emili, A., Lieberman, J., Shen, X., Buratowski, S., Haber, J. E., Durocher, D., Greenblatt, J. F., and Krogan, N. J. (2006) Nature 439(7075), 497-501
62. McManus, K. J., and Hendzel, M. J. (2005) Molecular biology of the cell 16(10), 5013-5025
63. Meng, L. H., Kohlhagen, G., Liao, Z. Y., Antony, S., Sausville, E., and Pommier, Y. (2005) Cancer research 65(12), 5337-5343
64. Petrini, J. H., and Stracker, T. H. (2003) Trends in cell biology 13(9), 458-462
65. Reitsema, T., Klokov, D., Banath, J. P., and Olive, P. L. (2005) DNA repair 4(10), 1172-1181
66. Tanaka, T., Halicka, H. D., Huang, X., Traganos, F., and Darzynkiewicz, Z. (2006) Cell cycle (Georgetown, Tex 5(17), 1940-1945
67. Mirzoeva, O. K., and Petrini, J. H. (2003) Mol Cancer Res 1(3), 207-218
68. Halicka, H. D., Huang, X., Traganos, F., King, M. A., Dai, W., and Darzynkiewicz, Z. (2005) Cell cycle (Georgetown, Tex 4(2), 339-345
69. Luo, Q., Yang, J., Zeng, Q. L., Zhu, X. M., Qian, Y. L., and Huang, H. F. (2006) Biology of reproduction 75(5), 673-680
70. Jackson, S. P. (2002) Carcinogenesis 23(5), 687-696
71. van Gent, D. C., Hoeijmakers, J. H., and Kanaar, R. (2001) Nat Rev Genet 2(3), 196-206
72. Blasina, A., Price, B. D., Turenne, G. A., and McGowan, C. H. (1999) Curr Biol 9(19), 1135-1138
73. Sarkaria, J. N., Busby, E. C., Tibbetts, R. S., Roos, P., Taya, Y., Karnitz, L. M., and Abraham, R. T. (1999) Cancer research 59(17), 4375-4382
74. O'Driscoll, M., Ruiz-Perez, V. L., Woods, C. G., Jeggo, P. A., and Goodship, J. A.
(2003) Nat Genet 33(4), 497-501
75. Yang, J., Yu, Y., Hamrick, H. E., and Duerksen-Hughes, P. J. (2003) Carcinogenesis 24(10), 1571-1580
76. Daniel, R., Marusich, E., Argyris, E., Zhao, R. Y., Skalka, A. M., and Pomerantz, R. J. (2005) J Virol 79(4), 2058-2065
77. Rowley, R., Martin, J. H., and Leeper, D. B. (1988) Radiation research 113(1), 58-70
78. Collis, S. J., DeWeese, T. L., Jeggo, P. A., and Parker, A. R. (2005) Oncogene 24(6), 949-961
79. Powis, G., Bonjouklian, R., Berggren, M. M., Gallegos, A., Abraham, R., Ashendel, C., Zalkow, L., Matter, W. F., Dodge, J., Grindey, G., and et al. (1994) Cancer research 54(9), 2419-2423
80. Yano, H., Nakanishi, S., Kimura, K., Hanai, N., Saitoh, Y., Fukui, Y., Nonomura, Y., and Matsuda, Y. (1993) The Journal of biological chemistry 268(34), 25846-25856
81. Rowley, R. (1992) Radiation research 129(2), 224-227
82. Nishijima, H., Nishitani, H., Saito, N., and Nishimoto, T. (2003) Genes Cells 8(5), 423-435
83. Wharton, W., and Goz, B. (1979) Biochem Pharmacol 28(6), 763-768
84. Wells, J. N., and Miller, J. R. (1988) Methods Enzymol 159, 489-496
85. Wang, H., Wang, X., Iliakis, G., and Wang, Y. (2003) Radiation research 159(3), 420-425
86. Wang, X., Wang, H., Iliakis, G., and Wang, Y. (2003) Radiation research 159(3), 426-432
87. Mirzayans, R., Severin, D., and Murray, D. (2006) Int J Radiat Oncol Biol Phys 66(5), 1498-1505
88. Kim, S. J., Ko, C. B., Park, C., Kim, B. R., Sung, T. H., Koh, D. H., Kim, N. S., Oh, K. J., Chung, S. Y., and Park, R. (2005) Archives of biochemistry and biophysics 444(2), 121-129
89. Matsuoka, S., Ballif, B. A., Smogorzewska, A., McDonald, E. R., 3rd, Hurov, K. E., Luo, J., Bakalarski, C. E., Zhao, Z., Solimini, N., Lerenthal, Y., Shiloh, Y., Gygi, S. P., and Elledge, S. J. (2007) Science (New York, N.Y 316(5828), 1160-1166
1. Tannheimer, S. L., Ethier, S. P., Caldwell, K. K., and Burchiel, S. W. (1998) Carcinogenesis 19(7), 1291-1297
2. Yoshii, S., Tanaka, M., Otsuki, Y., Fujiyama, T., Kataoka, H., Arai, H., Hanai, H., and Sugimura, H. (2001) Molecular and cellular biology 21(20), 6796-6807
3. Hussain, S. P., Amstad, P., Raja, K., Sawyer, M., Hofseth, L., Shields, P. G., Hewer, A., Phillips, D. H., Ryberg, D., Haugen, A., and Harris, C. C. (2001) Cancer research 61(17), 6350-6355
4. Kassie, F., Anderson, L. B., Higgins, L., Pan, Y., Matise, I., Negia, M., Upadhyaya, P., Wang, M., and Hecht, S. S. (2008) Carcinogenesis 29(3), 610-619
5. Olden, K., and Wilson, S. (2000) Nature reviews 1(2), 149-153
6. Peakall, D., and Shugart, L. (2002) Ecotoxicology (London, England) 11(1), 7
7. Akerman, G. S., Rosenzweig, B. A., Domon, O. E., McGarrity, L. J., Blankenship, L. R., Tsai, C. A., Culp, S. J., MacGregor, J. T., Sistare, F. D., Chen, J. J., and Morris, S. M. (2004) Mutation research 549(1-2), 43-64
8. Luo, W., Fan, W., Xie, H., Jing, L., Ricicki, E., Vouros, P., Zhao, L. P., and Zarbl, H. (2005) Chemical research in toxicology 15(4), 619-629
9．俞利荣，曾嵘，夏其昌．(1998) 生命的化学 18(6)，4-9
10. Patterson, S. D., and Aebersold, R. H. (2003) Nature genetics 33 Suppl, 311-323
11. O'Farrell, P. H. (1975) The Journal of biological chemistry 250(10), 4007-4021
12. Shen, W., Liu, H., and Yu, Y. (2007) Journal of proteome research 6(12), 4737-4748
13. Shen, W., Liu, H., and Yu, Y. (2008) Proteomics 8(17), 3450-3468
14. Gao, Z., Jin, J., Yang, J., and Yu, Y. (2004) Mutation research 550(1-2), 11-24
15. Yan, J. X., Wait, R., Berkelman, T., Harry, R. A., Westbrook, J. A., Wheeler, C. H., and Dunn, M. J. (2000) Electrophoresis 21(17), 3666-3672
16. Filippov, V., Schmidt, E. L., Filippova, M., and Duerksen-Hughes, P. J. (2008) Gene 420(1), 34-41
17. Hole, A. K., Belkhiri, A., Snell, L. S., and Watson, P. H. (1997) Breast cancer research and treatment 43(2), 165-173
18. Filippov, V., Filippova, M., and Duerksen-Hughes, P. J. (2007) Cancer research 67(16), 7621-7630
19. Sinclair, J., Weeks, M., Butt, A., Worthington, J. L., Akpan, A., Jones, N., Waterfield, M., Allanand, D., and Timms, J. F. (2006) Proteomics 6(17), 4755-4764
20. Taddei, A., Hediger, F., Neumann, F. R., and Gasser, S. M. (2004) Annual review of genetics 38, 305-345
21. Moir, R. D., Yoon, M., Khuon, S., and Goldman, R. D. (2000) The Journal of cell biology 151(6), 1155-1168
22. Belmont, A. S., Zhai, Y., and Thilenius, A. (1993) The Journal of cell biology 123(6 Pt 2),1671-1685
23. Stuurman, N., Heins, S., and Aebi, U. (1998) Journal of structural biology 122(1-2), 42-66
24. Rober, R. A., Weber, K., and Osbom, M. (1989) Development (Cambridge, England) 105(2),365-378
25. Rober, R. A., Gieseler, R. K., Peters, J. H., Weber, K., and Osbom, M. (1990) Experimental cell research 190(2), 185-194
26. Shumaker, D. K., Kuczmarski, E. R., and Goldman, R. D. (2003) Current opinion in cell biology 15(3), 358-366
27. Gruenbaum, Y., Goldman, R. D., Meyuhas, R., Mills, E., Margalit, A., Fridkin, A., Dayani, Y., Prokocimer, M., and Enosh, A. (2003) International review of cytology 226, 1-62
28. Gruenbaum, Y., Margalit, A., Goldman, R. D., Shumaker, D. K., and Wilson, K. L. (2005) Nature reviews 6(1), 21-31
29. Meier, J., Campbell, K. H., Ford, C. C., Stick, R., and Hutchison, C. J. (1991) Journal of cell science 98 ( Pt 3), 271-279
30. Sparta, T. P., Goldman, A. E., Wang, C., Huang, S., and Goldman, R. D. (2002) The Journal of cell biology 156(4), 603-608
31. Manju, K., Muralikrishna, B., and Pamaik, V. K. (2006) Journal of cell science 119(Pt 13), 2704-2714
32. Liu, B., Wang, J., Chan, K. M., Tjia, W. M., Deng, W., Guan, X., Huang, J. D., Li, K. M., Chau, P. Y., Chen, D. J., Pei, D., Pendas, A. M., Cadinanos, J., Lopez-Otin, C., Tse, H. F., Hutchison, C., Chen, J., Cao, Y., Cheah, K. S., Tryggvason, K., and Zhou, Z. (2005) Nature medicine 11(7), 780-785
33. Lees-Miller, S. P. (2006) DNA repair 5(2), 286-289
34. Grabsch, H., Takeno, S., Parsons, W. J., Pomjanski, N., Boecking, A., Gabbert, H. E., and Mueller, W. (2003) The Journal of pathology 200(1), 16-22
35. Fang, Y., Liu, T., Wang, X., Yang, Y. M., Deng, H., Kunicki, J., Traganos, F., Darzynkiewicz, Z., Lu, L., and Dai, W. (2006) Oncogene 25(25), 3598-3605
36. Sudakin, V., Chan, G. K., and Yen, T. J. (2001) The Journal of cell biology 154(5), 925-936
37. Diaz-Martinez, L. A., and Yu, H. (2007) Cell division 2, 23
38. Fang, G. (2002) Molecular biology of the cell 13(3), 755-766
39. Hardwick, K. G., Johnston, R. C., Smith, D. L., and Murray, A. W. (2000) The Journal of cell biology 145(5), 871-882
40. Greene, L. M., Campiani, G., Lawler, M., Williams, D. C., and Zisterer, D. M. (2008) Molecular pharmacology 73(2), 419-430
41. Zhang, S., Schlott, B., Gorlach, M., and Grosse, F. (2004) Nucleic acids research 32(1), 1-10
42. Lee, S. Y., Park, J. H., Kim, S., Park, E. J., Yun, Y., and Kwon, J. (2005) The Biochemical journal 388(Pt 1), 7-15
43. Moumen, A., Masterson, P., O'Connor, M. J., and Jackson, S. P. (2005) Cell 123(6), 1065-1078
44. Sheikh, M. S., Carrier, F., Papathanasiou, M. A., Hollander, M. C., Zhan, Q., Yu, K., and Fornace, A. J., Jr. (1997) The Journal of biological chemistry 272(42), 26720-26726
45. Yang, C., and Carrier, F. (2001) The Journal of biological chemistry 276(50), 47277-47284
46. Brand, M., Moggs, J. G., Oulad-Abdelghani, M., Lejeune, F., Dilworth, F. J., Stevenin, J., Almouzni, G., and Tora, L. (2001) The EMBO journal 20(12), 3187-3196
47. Matsuoka, S., Ballif, B. A., Smogorzewska, A., McDonald, E. R., 3rd, Hurov, K. E., Luo, J., Bakalarski, C. E., Zhao, Z., Solimini, N., Lerenthal, Y., Shiloh, Y., Gygi, S. P., and Elledge, S. J. (2007) Science (New York, N. Y316(5828), 1160-1166
48. Johnson, J. M., Castle, J., Garrett-Engele, P., Kan, Z., Loerch, P. M., Armour, C. D., Santos, R., Schadt, E. E., Stoughton, R., and Shoemaker, D. D. (2003) Science (New York, N. Y 302(5653), 2141-2144
49. Thorburn, A. (2004) Cellular signalling 16(2), 139-144
50. Hill, L. L., Ouhtit, A., Loughlin, S. M., Kripke, M. L., Ananthaswamy, H. N., and Owen-Schaub, L. B. (1999)Science (New York, N. Y 285(5429), 898-900
51. Mo, Y. Y., and Beck, W. T. (1999) Molecular pharmacology 55(2), 216-222
52. Chen, C., Chang, M. C., Hsieh, R. K., Chang, Y. F., Lin, J., and Tsan, K. W. (2005) Leukemia & lymphoma 46(12), 1785-1795
53. Li, C., Kato, M., Shiue, L., Shively, J. E., Ares, M., Jr., and Lin, R. J. (2006) Cancer research 66(4), 1990-1999
54. Wang, H., Guan, J., Wang, H., Perrault, A. R., Wang, Y., and Iliakis, G. (2001) Cancer research 61(23), 8554-8563
55. Din, S., Brill, S. J., Fairman, M. P., and Stillman, B. (1990) Genes & development 4(6), 968-977
56. Dutta, A., and Stillman, B. (1992) The EMBO journal 11(6), 2189-2199
57. Ogawa, K., Utsunomiya, T., Mimori, K., Tanaka, Y., Tanaka, F., Inoue, H., Murayama, S., and Mori, M. (2004) British journal of cancer 91(2), 282-286
58. Gartner, W., Rossbacher, J., Zierhut, B., Daneva, T., Base, W., Weissel, M., Waldhausl, W., Pastemack, M. S., and Wagner, L. (2003) Cell motility and the cytoskeleton 56(2), 79-93
59. Doyon, Y., Selleck, W., Lane, W. S., Tan, S., and Cote, J. (2004) Molecular and cellular biology 24(5), 1884-1896
60. Cowling, V. H., and Cole, M. D. (2006) Seminars in cancer biology 16(4), 242-252
61. Wang, X., Chen, C. F., Baker, P. R., Chen, P. L., Kaiser, P., and Huang, L. (2007) Biochemistry 46(11), 3553-3565
62. Roessler, M., Rollinger, W., Mantovani-Endl, L., Hagmann, M. L., Palme, S., Berndt, P., Engel, A. M., Pfeffer, M., Karl, J., Bodenmuller, H., Ruschoff, J., Henkel, T., Rohr, G., Rossol, S., Rosch, W., Langen, H., Zolg, W., and Tacke, M. (2006)Mol Cell Proteomics 5(11), 2092-2101
63. Hall, P. A., Jung, K., Hillan, K. J., and Russell, S. E. (2005) The Journal of pathology 206(3), 269-278
64. Montagna, C., Lyu, M. S., Hunter, K., Lukes, L., Lowther, W., Reppert, T., Hissong, B., Weaver, Z., and Ried, T. (2003) Cancer research 63(9), 2179-2187
1. Harper, J. W., and Elledge, S. J. (2007) Molecular cell 28(5), 739-745
2. Petrini, J. H., and Stracker, T. H. (2003) Trends in cell biology 13(9), 458-462
3. Lukas, C., Falck, J., Bartkova, J., Bartek, J., and Lukas, J. (2003) Nature cell biology 5(3), 255-260
4. Zhou, B. B., and Elledge, S. J. (2000) Nature 408(6811), 433-439
5. Mirzoeva, O. K., and Petrini, J. H. (2001) Molecular and cellular biology 21(1), 281-288
6. Paull, T. T., Rogakou, E. P., Yamazaki, V., Kirchgessner, C. U., Gellert, M., and Bonner, W. M. (2000) Curr Biol 10(15), 886-895
7. Rogakou, E. P., Boon, C., Redon, C., and Bonner, W. M. (1999) The Journal of cell biology 146(5), 905-916
8. Mirzoeva, O. K., and Petrini, J. H. (2003) Mol Cancer Res 1(3), 207-218
9. Fernandez-Capetillo, O., Mahadevaiah, S. K., Celeste, A., Romanienko, P. J., Camerini-Otero, R. D., Bonner, W. M., Manova, K., Burgoyne, P., and Nussenzweig, A. (2003) Developmental cell 4(4), 497-508
10. Lou, Z., Minter-Dykhouse, K., Wu, X., and Chen, J. (2003) Nature 421(6926), 957-961
11. Xu, X., and Stern, D. F. (2003) The Journal of biological chemistry 278(10), 8795-8803
12. Goldberg, M., Stucki, M., Falck, J., D'Amours, D., Rahman, D., Pappin, D., Bartek, J., and Jackson, S. P. (2003)Nature 421 (6926), 952-956
13. Burma, S., Chen, B. P., Murphy, M., Kurimasa, A., and Chen, D. J. (2001) The Journal of biological chemistry 276(45), 42462-42467
14. Stewart, G. S., Wang, B., Bignell, C. R., Taylor, A. M., and Elledge, S. J. (2003) Nature 421 (6926), 961-966
15. Downs, J. A. (2007) Oncogene 26(56), 7765-7772
16. van Attikum, H., and Gasser, S. M. (2005) Nature reviews 6(10), 757-765
17. Costelloe, T., Fitzgerald, J., Murphy, N. J., Flaus, A., and Lowndes, N. F. (2006) Experimental cell research 312(14), 2677-2686
18. Alami, R., Fan, Y., Pack, S., Sonbuchner, T. M., Besse, A., Lin, Q., Greally, J. M., Skoultchi, A. I., and Bouhassira, E. E. (2003) Proceedings of the National Academy of Sciences of the United States of America 100(10), 5920-5925
19. Fan, Y., Nikitina, T., Zhao, J., Fleury, T. J., Bhattacharyya, R., Bouhassira, E. E., Stein, A., Woodcock, C. L., and Skoultchi, A. I. (2005) Cell 123(7), 1199-1212
20. Konishi, A., Shimizu, S., Hirota, J., Takao, T., Fan, Y., Matsuoka, Y., Zhang, L., Yoneda, Y., Fujii, Y., Skoultchi, A. I., and Tsujimoto, Y. (2003) Cell 114(6), 673-688
21. Funayama, R., Saito, M., Tanobe, H., and Ishikawa, F. (2006) The Journal of cell biology 175(6), 869-880
22. Campisi, J. (2005) Science (New York, N.Y 309(5736), 886-887
23. Reeves, R., and Adair, J. E. (2005) DNA repair 4(8), 926-938
24. Travers, A. A. (2003) EMBO reports 4(2), 131-136
25. Yamanaka, S., Katayama, E., Yoshioka, K., Nagaki, S., Yoshida, M., and Teraoka, H. (2002) Biochemical and biophysical research communications 292(1), 268-273
26. Celeste, A., Petersen, S., Romanienko, P. J., Fernandez-Capetillo, O., Chen, H. T., Sedelnikova, O. A., Reina-San-Martin, B., Coppola, V., Meffre, E., Difilippantonio, M. J., Redon, C., Pilch, D. R., Olaru, A., Eckhaus, M., Camerini-Otero, R. D., Tessarollo, L., Livak, F., Manova, K., Bonner, W. M., Nussenzweig, M. C., and Nussenzweig, A. (2002) Science (New York, N. Y 296(5569), 922-927
27. Jha, S., Shibata, E., and Dutta, A. (2008) Molecular and cellular biology 28(8), 2690-2700
28. Celeste, A., Fernandez-Capetillo, O., Kruhlak, M. J., Pilch, D. R., Staudt, D. W., Lee, A., Bonner, R. F., Bonner, W. M., and Nussenzweig, A. (2003) Nature cell biology 5(7), 675-679
29. Shroff, R., Arbel-Eden, A., Pilch, D., Ira, G., Bonner, W. M., Petrini, J. H., Haber, J. E., and Lichten, M. (2004) Curr Biol 14(19), 1703-1711
30. Lukas, C., Melander, F., Stucki, M., Falck, J., Bekker-Jensen, S., Goldberg, M., Lerenthal, Y., Jackson, S. P., Bartek, J., and Lukas, J. (2004) The EMBO journal 23(13), 2674-2683
31. Downs, J. A., Allard, S., Jobin-Robitaille, O., Javaheri, A., Auger, A., Bouchard, N., Kron, S. J., Jackson, S. P., and Cote, J. (2004) Molecular cell 16(6), 979-990
32. Soutoglou, E., and Misteli, T. (2008) Science (New York, N.Y 320(5882), 1507-1510
33. Bonilla, C. Y., Melo, J. A., and Toezyski, D. P. (2008) Molecular cell 30(3), 267-276
34. Wood, J. L., and Chen, J. (2008) Trends in cell biology 18(10), 451-455
1. Tatsushi Toyookaa and Yuko Ibuki, a. (2007) Environmental Toxicology and Pharmacology 23, 256-263
2. Bostrom, C. E., Gerde, P., Hanberg, A., Jernstrom, B., Johansson, C., Kyrklund, T., Rarmug, A., Tornqvist, M., Victorin, K., and Westerholm, R. (2002) Environmental health perspectives 110 Suppl 3, 451-488
3. Toyooka, T., Ohnuki, G., and Ibuki, Y. (2008) Mutation research 650(2), 132-139
4. White, P. A., and Claxton, L. D. (2004) Mutation research 567(2-3), 227-345
5. Xue, W., and Warshawsky, D. (2005) Toxicology and applied pharmacology 206(1), 73-93
6. NAKAGAWA Y(Hatano Res. Inst., K., Jpn) TAKIGAWA Y(Hatano Res. Inst., Kanagawa, Jpn) TANAKA N(Hatano Res. Inst., Kanagawa, Jpn) (2001) Environmental Mutagen Research Communications 23, 107-118
7. Dong, S., Fu, P. P., Shirsat, R. N., Hwang, H. M., Leszczynski, J., and Yu, H. (2002) Chemical research in toxicology 15(3), 400-407
8. tatsushi toyooka, y. i. (2007) enviornmental toxicology and pharmacology 23, 256-263
9. Yang, S. K. (1988) Biochemical pharmacology 37(1), 61-70
10. Levin, W., Buening, M. K., Wood, A. W., Chang, R. L., Kedzierski, B., Thakker, D. R., Boyd, D. R., Gadaginamath, G. S., Armstrong, R. N., Yagi, H., Karle, J. M., Slaga, T. J., Jerina, D. M., and Conney, A. H. (1980) The Journal of biological chemistry 255(19), 9067-9074
11. thakker, D. R., Yagi,H., levin,W.,. (1985) bioactivation of foreign compounds, academic press, new york, 177-242
12. ragan, E. G., Cavalieri,E.L., Tibbel,S.R.,. (1988) J. Am. Chem. Soc. 110, 4023-4029
13. Cavalieri, E. L., and Rogan, E. G. (1992) Pharmacology & therapeutics 55(2), 183-199
14. Xue, W., Zapien, D., and Warshawsky, D. (1999) Chemical research in toxicology 12(12), 1234-1239
15. Penning, T. M., Ohnishi, S. T., Ohnishi, T., and Harvey, R. G. (1996) Chemical research in toxicology 9(1), 84-92
16. Chung, H. S., Harvey, R. G., Armstrong, R. N., and Jarabak, J. (1987) The Journal of biological chemistry 262(26), 12448-12451
17. McCoull, K. D., Rindgen, D., Blair, I. A., and Penning, T. M. (1999) Chemical research in toxicology 12(3), 237-246
18. Penning, T. M., Burczynski, M. E., Hung, C. F., McCoull, K. D., Palackal, N. T., and Tsuruda, L. S. (1999) Chemical research in toxicology 12(1), 1-18
19. dipple, A. (1994), 107-129
20. Wolfe, A. R., Smith, T. J., and Meehan, T. (2004) Chemical research in toxicology 17(4), 476-491
21. Klinedinst, D. K., and Drinkwater, N. R. (1992) Molecular carcinogenesis 6(1), 32-42
22. Schaaper, R. M., Kunkel, T. A., and Loeb, L. A. (1983) Proceedings of the National Academy of Sciences of the United States of America 80(2), 487-491
23. Shou, M., Harvey, R. G., and Penning, T. M. (1993) Carcinogenesis 14(3), 475-482
24. Balu, N., Padgett, W. T., Lambert, G. R., Swank, A. E., Richard, A. M., and Nesnow, S. (2004) Chemical research in toxicology 17(6), 827-838
25. Beckman, K. B., and Ames, B. N. (1997) The Journal of biological chemistry 272(32), 19633-19636
26. Yu, H. (2002) Journal of environmental science and health 20(2), 149-183
27. Yu, H., Xia, Q., Yan, J., Herreno-Saenz, D., Wu, Y. S., Tang, I. W., and Fu, P. P. (2006) International journal of environmental research and public health 3(4), 348-354
28. RC Swartz, S. F., JO Lamberson, FA Cole. (1997) Environmental Toxicology and Chemistry 16, 2151-2157
29. Gao, D., Luo, Y., Guevara, D., Wang, Y., Rui, M., Goldwyn, B., Lu, Y., Smith, E. C., Lebwohl, M., and Wei, H. (2005) Free radical biology & medicine 39(9), 1177-1183
30. Gavrilov, B., Vezhenkova, I., Firsanov, D., Solovjeva, L., Svetlova, M., Mikhailov, V., and Tomilin, N. (2006) Biochemical and biophysical research communications 347(4), 1048-1052
31. Hung, H. S., Wu, W. J., Cheng, Y. W., Wu, T. C., Chang, K. L., and Lee, H. (2007) Mutation research 628(2), 107-116
32. Prise, K. M., Folkard, M., Kuosaite, V., Tartier, L., Zyuzikov, N., and Shao, C. (2006) Mutation research 597(1-2), 1-4
33. Dong, S., Hwang, H. M., Harrison, C., Holloway, L., Shi, X., and Yu, H. (2000) Bulletin of environmental contamination and toxicology 64(4), 467-474
34. Strniste, G. F., Martinez, E., Martinez, A. M., and Brake, R. J. (1980) Cancer research 40(2), 245-252
35. Utsumi, H., Kitani, H., Chang-Liu, C. M., and Elkind, M. M. (1987) Carcinogenesis 8(10), 1439-1444
36. Tuveson, R. W., Wang, G. R., Wang, T. P., and Kagan, J. (1990) Photochemistry and photobiology 52(5), 993-1002
37. Toyooka, T., Ibuki, Y., Takabayashi, F., and Goto, R. (2006) Environmental and molecular mutagenesis 47(1), 38-47
38. Toyooka, T., Ibuki, Y., Koike, M., Ohashi, N., Takahashi, S., and Goto, R. (2004) Biochemical and biophysical research communications 322(2), 631-636
39. Wang, L., Yan, J., Wang, S., Cohly, H., Fu, P. P., Hwang, H. M., and Yu, H. (2004) Mutation research 562(1-2), 143-150
40. Zhang, X., Wu, R. S., Fu, W., Xu, L., and Lain, P. K. (2004) Chemosphere 55(10), 1303-1308
41. Liu, Z., Lu, Y., Rosenstein, B., Lebwohl, M., and Wei, H. (1998) Biochemistry 37(28), 10307-10312