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CRL4DCAF12 regulation of MCMBP ensures optimal licensing of DNA replication

Author

Listed:
  • Anoop Kumar Yadav

    (Czech Academy of Sciences
    Masaryk University)

  • Alikhan Abdirov

    (Czech Academy of Sciences)

  • Katarina Ondruskova

    (Czech Academy of Sciences)

  • Simran Negi

    (Czech Academy of Sciences
    Masaryk University)

  • Kristina Jamrichova

    (Czech Academy of Sciences)

  • Karolina Kolarova

    (Czech Academy of Sciences
    Charles University)

  • Nikol Dibus

    (Czech Academy of Sciences)

  • Jana Krejci

    (Czech Academy of Sciences)

  • Hana Polasek-Sedlackova

    (Czech Academy of Sciences)

  • Lukas Cermak

    (Czech Academy of Sciences)

Abstract

The minichromosome maintenance (MCM2-7) protein complexes are central drivers of genome duplication. Distinct protein pools, parental and nascent MCMs, and their precise equilibrium are essential to sustain error-free DNA replication. However, the mechanism responsible for generating these pools and maintaining their equilibrium remains largely unexplored. Here, we identified CRL4DCAF12 as a factor controlling the assembly of nascent MCM complexes. During MCM biogenesis, MCMBP facilitates the assembly and transport of newly synthesized MCM3-7 subcomplexes into the nucleus. Once in the nucleus, the MCM2 subunit must be incorporated into the MCM3-7 subcomplex, while MCMBP needs to be removed. CRL4DCAF12 facilitates the degradation of MCMBP and thereby regulates the assembly of MCM2-7 complexes. The absence of CRL4DCAF12 adversely affects the level of chromatin-bound nascent MCMs, resulting in accelerated replication forks and replication stress. Collectively, our findings uncovered the molecular mechanism underlying nascent MCM production essential to counteract genome instability.

Suggested Citation

  • Anoop Kumar Yadav & Alikhan Abdirov & Katarina Ondruskova & Simran Negi & Kristina Jamrichova & Karolina Kolarova & Nikol Dibus & Jana Krejci & Hana Polasek-Sedlackova & Lukas Cermak, 2025. "CRL4DCAF12 regulation of MCMBP ensures optimal licensing of DNA replication," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64258-5
    DOI: 10.1038/s41467-025-64258-5
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