Transcription-coupled homologous recombination after oxidative damage

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• 作者：Leizhen Wei^a ; ^b ; Arthur Samuel Levine^a ; ^b ; Li Lan^a ; ^b ; ^{lil64@pitt.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：DSBs ; double strand breaks ; SSBs ; single strand breaks ; HR ; homologous recombination ; NHEJ ; non-homologous end-joining ; CSA ; Cockayne syndrome protein A ; CSB ; Cockayne syndrome protein B ; TC-NER ; transcription-coupled nucleotide excision repair ; TC-DSBR ; transcription may be coupled to double strand break repair ; ICLs ; interstrand crosslinks ; TC-HR ; transcription-coupled homologous recombination ; TA ; transcriptionally active ; TI ; transcriptionally inactive ; HDR ; homology-directed repair ; KR ; Kil
• 刊名：DNA Repair
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：44
• 期：Complete
• 页码：76-80
• 全文大小：1163 K

文摘

Oxidative DNA damage induces genomic instability and may lead to mutagenesis and carcinogenesis. As severe blockades to RNA polymerase II (RNA POLII) during transcription, oxidative DNA damage and the associated DNA strand breaks have a profoundly deleterious impact on cell survival. To protect the integrity of coding regions, high fidelity DNA repair at a transcriptionally active site in non-dividing somatic cells, (i.e., terminally differentiated and quiescent/G0 cells) is necessary to maintain the sequence integrity of transcribed regions. Recent studies indicate that an RNA-templated, transcription-associated recombination mechanism is important to protect coding regions from DNA damage-induced genomic instability. Here, we describe the discovery that G1/G0 cells exhibit Cockayne syndrome (CS) B (CSB)-dependent assembly of homologous recombination (HR) factors at double strand break (DSB) sites within actively transcribed regions. This discovery is a challenge to the current dogma that HR occurs only in S/G2 cells where undamaged sister chromatids are available as donor templates.