Background
The minichromosome maintenance 2-7 proteins are a family of six related proteins required for initiation and elongation of DNA replication. MCM2-7 bind together to form the heterohexameric MCM complex that is thought to act as a replicative helicase at the DNA replication fork. This complex is a key component of the pre-replication complex. Cdc6 and CDT1 recruit the MCM complex to the origin recognition complex during late mitosis/early G1 phase forming the pre-RC and licensing the DNA for replication. Licensing of the chromatin permits the DNA to replicate only once per cell cycle, thereby helping to ensure that genetic alterations and malignant cell growth do not occur. Phosphorylation of the MCM2, MCM3, MCM4, and MCM6 subunits appears to regulate MCM complex activity and the initiation of DNA synthesis. CDK1 phosphorylation of MCM3 at Ser112 during late mitosis/early G1 phase has been shown to initiate complex formation and chromatin loading in vitro. Phosphorylation of MCM2 at serine 139 by cdc7/dbf4 coincides with the initiation of DNA replication. MCM proteins are removed during DNA replication, causing chromatin to become unlicensed through inhibition of pre-RC reformation. Studies have shown that the MCM complex is involved in checkpoint control by protecting the structure of the replication fork and assisting in restarting replication by recruiting checkpoint proteins after arrest.
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