RNA–DNA hybrids and the convergence with DNA repair

Abstract

The repair of DNA double-strand breaks occurs through a series of defined steps that are evolutionarily conserved and well-understood in most experimental organisms. However, it is becoming increasingly clear that repair does not occur in isolation from other DNA transactions. Transcription of DNA produces topological changes, RNA species, and RNA-dependent protein complexes that can dramatically influence the efficiency and outcomes of DNA double-strand break repair. The transcription-associated history of several double-strand break repair factors is reviewed here, with an emphasis on their roles in regulating R-loops and the emerging role of R-loops in coordination of repair events. Evidence for nucleolytic processing of R-loops is also discussed, as well as the molecular tools commonly used to measure RNA-DNA hybrids in cells.

Keywords:

• DNA repair
• transcription
• R-loop
• RNA–DNA hybrid
• Brca1
• Brca2
• CtIP

Acknowledgements

Thanks to Andrés Aguilera, members of the Paull and Finkelstein laboratories, and reviewers for helpful comments and suggestions. Apologies to colleagues whose studies could not be included due to space limitations.

Disclosure statement

No potential conflict of interest was reported by the author.

Additional information

Funding

This study was financially supported in part by the Cancer Prevention and Research Institute of Texas.