CRL4<sup>DCAF12</sup> regulation of MCMBP ensures optimal licensing of DNA replication.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41145411.
- Also identified by DOI 10.1038/s41467-025-64258-5 and PMC identifier 12559739.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 CRL4<sup>DCAF12</sup> 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. CRL4<sup>DCAF12</sup> facilitates the degradation of MCMBP and thereby regulates the assembly of MCM2-7 complexes. The absence of CRL4<sup>DCAF12</sup> 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.
Medical subject headings
- DNA Replication
- Minichromosome Maintenance Proteins
- Cell Cycle Proteins