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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月1日

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  • Amador Romero-Franco,
  • Cintia Checa-Rodríguez,
  • Sonia Jimeno,
  • Maikel Castellano-Pozo,
  • Paula Aguilera,
  • Hector Miras,
  • Amadeo Wals,
  • Silvia Jimeno-González,
  • Andres Joaquin Lopez-Contreras,
  • Pablo Huertas

摘要

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.