Circadian regulation of homologous recombination by cryptochrome1-mediated dampening of DNA end resection
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.
Authors
- Maikel Castellano‐Pozo (ORCID: https://orcid.org/0000-0003-4134-9025)
- Cintia Checa-Rodríguez (ORCID: https://orcid.org/0000-0003-4838-7323)
- Silvia Jimeno-González (ORCID: https://orcid.org/0000-0002-6223-9573)
- Amador Romero-Franco (ORCID: https://orcid.org/0000-0003-3212-1643)
- Pablo Huertas (ORCID: https://orcid.org/0000-0002-1756-4449)
- Sonia Jimeno (ORCID: https://orcid.org/0000-0002-7034-0081)
- Amadeo Wals-Zurita (ORCID: https://orcid.org/0000-0002-8869-1015)
- Andrés J. López‐Contreras (ORCID: https://orcid.org/0000-0002-5517-7327)
- Paula Aguilera (ORCID: https://orcid.org/0000-0002-6937-8517)
- H. Miras (ORCID: https://orcid.org/0000-0002-0534-3657)
Institutions
- Hospital Universitario Virgen Macarena (ES)
- Instituto de Biomedicina de Sevilla (ES)
- Centro Andaluz de Biología Molecular y Medicina Regenerativa (ES)
- Hospital Universitario Virgen del Rocío (ES)
- Universidad de Sevilla (ES)
- Universidad Pablo de Olavide (ES)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1038/s41467-025-65854-1
- Citations
- 1
- Primary Topic
- Circadian rhythm and melatonin
- Type
- article
- Field-Weighted Citation Impact
- 0.91
Funders
- Consejería de Transformación Económica, Industria, Conocimiento y Universidades
- Junta de Andalucía
- Agencia Estatal de Investigación