Article
Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability
Author/s | Sollier, Julie
Townsend Stork, Caroline García Rubio, María Luisa Aguilera López, Andrés |
Department | Universidad de Sevilla. Departamento de Genética |
Publication Date | 2014 |
Deposit Date | 2017-12-12 |
Published in |
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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 ... 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. |
Citation | Sollier, J., Townsend Stork, C., García Rubio, M.L. y Aguilera López, A. (2014). Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability. Molecular Cell, 56 (6), 777-785. |
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