Repair of G1 induced DNA double-strand breaks in S-G2/M by alternative NHEJ

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• dc.contributor.author Yu, Wei
• dc.contributor.author Lescale, Chloé
• dc.contributor.author Babin, Loelia
• dc.contributor.author Bedora-Faure, Marie
• dc.contributor.author Lenden-Hasse, Hélène
• dc.contributor.author Baron, Ludivine
• dc.contributor.author Demangel, Caroline
• dc.contributor.author Yélamos López, José
• dc.contributor.author Brunet, Erika
• dc.contributor.author Deriano, Ludovic
• dc.date.accessioned 2022-01-13T08:54:08Z
• dc.date.available 2022-01-13T08:54:08Z
• dc.date.issued 2020
• dc.description.abstract The alternative non-homologous end-joining (NHEJ) pathway promotes DNA double-strand break (DSB) repair in cells deficient for NHEJ or homologous recombination, suggesting that it operates at all stages of the cell cycle. Here, we use an approach in which DNA breaks can be induced in G1 cells and their repair tracked, enabling us to show that joining of DSBs is not functional in G1-arrested XRCC4-deficient cells. Cell cycle entry into S-G2/M restores DSB repair by Pol θ-dependent and PARP1-independent alternative NHEJ with repair products bearing kilo-base long DNA end resection, micro-homologies and chromosome translocations. We identify a synthetic lethal interaction between XRCC4 and Pol θ under conditions of G1 DSBs, associated with accumulation of unresolved DNA ends in S-G2/M. Collectively, our results support the conclusion that the repair of G1 DSBs progressing to S-G2/M by alternative NHEJ drives genomic instability and represent an attractive target for future DNA repair-based cancer therapies.
• dc.format.mimetype application/pdf
• dc.identifier.citation Yu W, Lescale C, Babin L, Bedora-Faure M, Lenden-Hasse H, Baron L, et al. Repair of G1 induced DNA double-strand breaks in S-G2/M by alternative NHEJ. Nat Commun. 2020 Oct 16; 11(1): 5239. DOI: 10.1038/s41467-020-19060-w
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-020-19060-w
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/52212
• dc.language.iso eng
• dc.publisher Nature Research
• dc.rights Copyright © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other ADN--Dany
• dc.subject.other Càncer--Tractament
• dc.title Repair of G1 induced DNA double-strand breaks in S-G2/M by alternative NHEJ
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion