Open AccessBRCA1 and RNAi factors promote repair mediated by small RNAs and PALB2–RAD52
Author(s) -
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
Publication year - 2021
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-020-03150-2
Subject(s) - biology , rna interference , dna repair , genome instability , microbiology and biotechnology , dna , rna , dna damage , small interfering rna , rad52 , genetics , rad51 , gene
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 7 . 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 8 . 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.