生物
RNA干扰
DNA修复
基因组不稳定性
细胞生物学
DNA
核糖核酸
DNA损伤
小干扰RNA
RAD52
遗传学
雷达51
基因
作者
Elodie Hatchi,Liana Goehring,Serena Landini,Konstantina Skourti-Stathaki,Derrick K. DeConti,Fieda Abderazzaq,Priyankana Banerjee,Timothy M. Demers,Yaoyu E. Wang,John Quackenbush,David M. Livingston
出处
期刊:Nature
[Springer Nature]
日期:2021-02-03
卷期号:591 (7851): 665-670
被引量:30
标识
DOI:10.1038/s41586-020-03150-2
摘要
Strong connections exist between R-loops (three-stranded structures harbouring an RNA:DNA hybrid and a displaced single-strand DNA), genome instability and human disease1-5. Indeed, R-loops are favoured in relevant genomic regions as regulators of certain physiological processes through which homeostasis is typically maintained. For example, transcription termination pause sites regulated by R-loops can induce the synthesis of antisense transcripts that enable the formation of local, RNA interference (RNAi)-driven heterochromation6. Pause sites are also protected against endogenous single-stranded DNA breaks by BRCA17. Hypotheses about how DNA repair is enacted at pause sites include a role for RNA, which is emerging as a normal, albeit unexplained, regulator of genome integrity8. Here we report that a species of single-stranded, DNA-damage-associated small RNA (sdRNA) is generated by a BRCA1-RNAi protein complex. sdRNAs promote DNA repair driven by the PALB2-RAD52 complex at transcriptional termination pause sites that form R-loops and are rich in single-stranded DNA breaks. sdRNA repair operates in both quiescent (G0) and proliferating cells. Thus, sdRNA repair can occur in intact tissue and/or stem cells, and may contribute to tumour suppression mediated by BRCA1.
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