BRCA1 and RNAi factors promote repair mediated by small RNAs and PALB2–RAD52
Strong connections exist between R-loops (three-stranded structures harbouring an RNA:DNA hybrid and a displaced single-strand DNA), genome instability and human disease 1 – 5 . Indeed, R-loops are favoured in relevant genomic regions as regulators of certain physiological processes through which ho...
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Published in | Nature (London) Vol. 591; no. 7851; pp. 665 - 670 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
25.03.2021
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | Strong connections exist between R-loops (three-stranded structures harbouring an RNA:DNA hybrid and a displaced single-strand DNA), genome instability and human disease
1
–
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 heterochromation
6
. Pause sites are also protected against endogenous single-stranded DNA breaks by BRCA1
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. 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 integrity
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. 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.
Single-stranded, DNA-damage-associated small RNAs generated by a BRCA1–RNA-interference complex promote PALB2–RAD52-mediated DNA repair at transcriptional termination pause sites that contain R-loops and are rich in single-stranded DNA breaks in both quiescent and proliferating cells. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0028-0836 1476-4687 |
DOI: | 10.1038/s41586-020-03150-2 |