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Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/121631
Título

Transcription-Coupled Nucleotide Excision Repair Factors Promote R-Loop-Induced Genome Instability

AutorSollier, Julie; Townsend Stork, Caroline; García-Rubio, María L. ; Paulsen, Renee D.; Aguilera, Andrés ; Cimprich, Karlene A.
Fecha de publicación26-nov-2014
EditorElsevier
CitaciónMolecular Cell 56(6): 777-785 (2014)
ResumenR-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.
Versión del editorhttp://dx.doi.org/10.1016/j.molcel.2014.10.020
URIhttp://hdl.handle.net/10261/121631
DOI10.1016/j.molcel.2014.10.020
ISSN1097-2765
E-ISSN1097-4164
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