Abstract:
:R-loops, consisting of an RNA-DNA hybrid and displaced single-stranded DNA, are physiological structures that regulate various cellular processes occurring on chromatin. Intriguingly, changes in R-loop dynamics have also been associated with DNA damage accumulation and genome instability; however, the mechanisms underlying R-loop-induced DNA damage remain unknown. Here we demonstrate in human cells that R-loops induced by the absence of diverse RNA processing factors, including the RNA/DNA helicases Aquarius (AQR) and Senataxin (SETX), or by the inhibition of topoisomerase I, are actively processed into DNA double-strand breaks (DSBs) by the nucleotide excision repair endonucleases XPF and XPG. Surprisingly, DSB formation requires the transcription-coupled nucleotide excision repair (TC-NER) factor Cockayne syndrome group B (CSB), but not the global genome repair protein XPC. These findings reveal an unexpected and potentially deleterious role for TC-NER factors in driving R-loop-induced DNA damage and genome instability.
journal_name
Mol Celljournal_title
Molecular cellauthors
Sollier J,Stork CT,García-Rubio ML,Paulsen RD,Aguilera A,Cimprich KAdoi
10.1016/j.molcel.2014.10.020subject
Has Abstractpub_date
2014-12-18 00:00:00pages
777-85issue
6eissn
1097-2765issn
1097-4164pii
S1097-2765(14)00830-2journal_volume
56pub_type
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