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.
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