Circadian regulation of homologous recombination by cryptochrome1-mediated dampening of DNA end resection

[Data availability] All relevant data are included in the manuscript.Source data are provided with this paper. ChIP-seq data are deposited at GEO under the accession number GSE261427. All data is available from the authors upon request. Source data are provided with this paper.

Detalles Bibliográficos
Autores: Romero-Franco, Amador, Checa-Rodríguez, Cintia, Jimeno, Sonia, Castellano-Pozo, Maikel, Aguilera, Paula, Miras, Héctor, Wals-Zurita, Amadeo, Jimeno-González, Silvia, López-Contreras, Andrés J., Huertas, Pablo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/412688
Acceso en línea:http://hdl.handle.net/10261/412688
https://api.elsevier.com/content/abstract/scopus_id/105023452914
Access Level:acceso abierto
Palabra clave:Genomic instability
Homologous recombination
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dc.title.none.fl_str_mv Circadian regulation of homologous recombination by cryptochrome1-mediated dampening of DNA end resection
title Circadian regulation of homologous recombination by cryptochrome1-mediated dampening of DNA end resection
spellingShingle Circadian regulation of homologous recombination by cryptochrome1-mediated dampening of DNA end resection
Romero-Franco, Amador
Genomic instability
Homologous recombination
title_short Circadian regulation of homologous recombination by cryptochrome1-mediated dampening of DNA end resection
title_full Circadian regulation of homologous recombination by cryptochrome1-mediated dampening of DNA end resection
title_fullStr Circadian regulation of homologous recombination by cryptochrome1-mediated dampening of DNA end resection
title_full_unstemmed Circadian regulation of homologous recombination by cryptochrome1-mediated dampening of DNA end resection
title_sort Circadian regulation of homologous recombination by cryptochrome1-mediated dampening of DNA end resection
dc.creator.none.fl_str_mv Romero-Franco, Amador
Checa-Rodríguez, Cintia
Jimeno, Sonia
Castellano-Pozo, Maikel
Aguilera, Paula
Miras, Héctor
Wals-Zurita, Amadeo
Jimeno-González, Silvia
López-Contreras, Andrés J.
Huertas, Pablo
author Romero-Franco, Amador
author_facet Romero-Franco, Amador
Checa-Rodríguez, Cintia
Jimeno, Sonia
Castellano-Pozo, Maikel
Aguilera, Paula
Miras, Héctor
Wals-Zurita, Amadeo
Jimeno-González, Silvia
López-Contreras, Andrés J.
Huertas, Pablo
author_role author
author2 Checa-Rodríguez, Cintia
Jimeno, Sonia
Castellano-Pozo, Maikel
Aguilera, Paula
Miras, Héctor
Wals-Zurita, Amadeo
Jimeno-González, Silvia
López-Contreras, Andrés J.
Huertas, Pablo
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Commission
Agencia Estatal de Investigación (España)
Ministerio de Ciencia e Innovación (España)
Junta de Andalucía
Asociación Española Contra el Cáncer
Ministerio de Educación (España)
Checa-Rodríguez, Cintia [0000-0003-4838-7323]
Castellano-Pozo, Maikel [0000-0003-4134-9025]
Aguilera, Paula [0000-0002-6937-8517]
Miras, Héctor [0000-0002-0534-3657]
Wals-Zurita, Amadeo [0000-0002-8869-1015]
Jimeno-González, Silvia [0000-0002-6223-9573]
López-Contreras, Andrés J. [0000-0002-5517-7327]
Huertas, Pablo [0000-0002-1756-4449]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Genomic instability
Homologous recombination
topic Genomic instability
Homologous recombination
description [Data availability] All relevant data are included in the manuscript.Source data are provided with this paper. ChIP-seq data are deposited at GEO under the accession number GSE261427. All data is available from the authors upon request. Source data are provided with this paper.
publishDate 2025
dc.date.none.fl_str_mv 2025
2026
2026
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/412688
https://api.elsevier.com/content/abstract/scopus_id/105023452914
url http://hdl.handle.net/10261/412688
https://api.elsevier.com/content/abstract/scopus_id/105023452914
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The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1038/s41467-025-65854-1
https://doi.org/10.1038/s41467-025-65854-1
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spelling Circadian regulation of homologous recombination by cryptochrome1-mediated dampening of DNA end resectionRomero-Franco, AmadorCheca-Rodríguez, CintiaJimeno, SoniaCastellano-Pozo, MaikelAguilera, PaulaMiras, HéctorWals-Zurita, AmadeoJimeno-González, SilviaLópez-Contreras, Andrés J.Huertas, PabloGenomic instabilityHomologous recombination[Data availability] All relevant data are included in the manuscript.Source data are provided with this paper. ChIP-seq data are deposited at GEO under the accession number GSE261427. All data is available from the authors upon request. Source data are provided with this paper.Genomic stability maintenance requires the repair of DNA breaks in the most accurate fashion. So, an exquisite regulatory network controls the choice between different repair mechanisms to maximize genome integrity. This relies mostly at the level of DNA end resection, the initial steps of the homologous recombination. On the other hand, numerous cellular activities follow a 24 h oscillation known as the circadian cycle. Thus, we explored the regulation of the choice between different DNA break repair pathways along the circadian cycle. Here we show that in human cells DNA resection shows a circadian oscillation, with a peak at early morning followed by a partial and progressive reduction until late afternoon. Such regulation depends on the circadian clock core component CRY1, which modulates the anti-resection activity of CCAR2 to limit CtIP at nightfall. Additionally, such regulation requires DNA-PK-mediated phosphorylation of CRY1. Finally, this circadian regulation impacts cancer progression and response to radiation therapy of specific tumours.This work was funded by the R + D + I grants PID2019-104195G and PID2022-136791NB-I00 funded by MICIU/AEI/10.13039/501100011033/ FEDER/UE, the grant P18-RT-1204 from the Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía and the grant PRYGN246626HUER from the Asociación Española Contra el Cáncer. The mouse work in the ALC laboratory was funded by the R+D+I grant PID2020-119329RB-I00, the SJ lab is funded by the grant PID2022-140603NB-I00, and the SJG lab is funded by the grant PID2022-139253N, all three funded by MICIU/AEI/10.13039/501100011033/ FEDER/UE. MC-P is the recipient of an MSCA-IF-2020 (coDNAres) that covers his salary and part of the reagents. AR-F is funded with a FPU fellowship from the Spanish Ministry of Education and PA was supported by a postdoctoral fellowship from the Junta de Andalucía and the European Social Fund (202099908313486), and by a postdoctoral grant from the Scientific Foundation of the Spanish Association Against Cancer (POSTD234422AGUI). CABIMER is supported by the regional government of Andalucía (Junta de Andalucía). We thank José Carlos Reyes-Rosa for the critical reading of the manuscript. We also want to thank the Microscopy and Genomic Unit of CABIMER for their support in the experiments.Peer reviewedNature Publishing GroupEuropean CommissionAgencia Estatal de Investigación (España)Ministerio de Ciencia e Innovación (España)Junta de AndalucíaAsociación Española Contra el CáncerMinisterio de Educación (España)Checa-Rodríguez, Cintia [0000-0003-4838-7323]Castellano-Pozo, Maikel [0000-0003-4134-9025]Aguilera, Paula [0000-0002-6937-8517]Miras, Héctor [0000-0002-0534-3657]Wals-Zurita, Amadeo [0000-0002-8869-1015]Jimeno-González, Silvia [0000-0002-6223-9573]López-Contreras, Andrés J. [0000-0002-5517-7327]Huertas, Pablo [0000-0002-1756-4449]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202620262025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/412688https://api.elsevier.com/content/abstract/scopus_id/105023452914reponame:DIGITAL.CSIC. 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