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bioRxiv · 10.1101/2024.11.26.625391

CRL4DCAF12 regulation of MCMBP ensures optimal licensing of DNA replication

Yadav, A. K.·Abdirov, A.·Ondruskova, K.·Negi, S.·Kolarova, K.·Dibus, N.·Krejci, J.·Polasek-Sedlackova, H.·Cermak, L.
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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 replication1. However, the mechanism responsible for generating these pools and maintaining their equilibrium remains largely unexplored. Here, we identified CRL4DCAF12 as a new 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 nucleus2,3. 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 genome instability. Collectively, our findings uncovered the molecular mechanism underlying nascent MCM production essential to counteract genome instability and tumor formation.

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Yadav, A. K., Abdirov, A., Ondruskova, K., Negi, S., Kolarova, K., Dibus, N., Krejci, J., Polasek-Sedlackova, H., Cermak, L.. 2024-11-28. CRL4DCAF12 regulation of MCMBP ensures optimal licensing of DNA replication. https://doi.org/10.1101/2024.11.26.625391

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