The reference OMIM entry for this protein is 116945

Minichromosome maintenance complex component 2; mcm2
Minichromosome maintenance, s. cerevisiae, homolog of, 2
Mitotin
Cell division cycle-like 1; cdcl1
Nuclear protein bm28; bm28

DESCRIPTION

MCM2, also called CDCL1 and BM28, is a human nuclear protein that plays an important role in 2 crucial steps of the cell cycle, namely, onset of DNA replication and cell division (Mincheva et al., 1994). It is similar to members of the family of early S-phase proteins.

CLONING

The replication of DNA occurs only once per cell cycle in eukaryotes. Blow and Laskey (1988) attempted to explain this tight control by proposing the existence of a hypothetical licensing factor that would bind to chromatin during mitosis to permit DNA replication during the ensuing S phase in Xenopus egg extracts. Kubota et al. (1995), Chong et al. (1995), and Madine et al. (1995) identified a replication licensing activity in a complex containing MCM/P1 family proteins in Xenopus oocytes. Burkhart et al. (1995) showed that human MCM2 and MCM5 (602696) proteins form a complex. Hu et al. (1993) reported cDNA sequences for 5 MCM/P1 family members.

MAPPING

Using plasmid DNA containing the complete coding sequence of the CDCL1 gene as a probe for fluorescence in situ hybridization, Mincheva et al. (1994) mapped the gene to 3q21. From its localization, CDCL1 became a candidate for an oncogene affected by chromosomal breaks in acute myeloid leukemia (AML).

GENE FUNCTION

Tsuruga et al. (1997) reported the comparative analysis of the human MCM proteins MCM2, MCM3 (602693), MCM5, and MCM7 (600592). The 4 MCM proteins underwent unequal regulation, suggesting that they play somewhat distinct roles in the regulation of the mammalian cell cycle. The mRNA levels of these genes underwent cell cycle-dependent oscillations with a peak at G1/S phase; they may be regulated by E2F motifs (see E2F1; 189971), 2 of which were detected in the 5-prime regulatory region of the MCM5 gene. In contrast, the levels of these MCM proteins remained rather constant during the HeLa cell cycle. However, their levels gradually increased in a variable manner as normal cells progressed from G0 into the G1/S phase. In the G0 stage, the MCM2 and MCM5 proteins were much less abundant than the MCM7 and MCM3 proteins. This suggests that the MCM proteins are not present in stoichiometric amounts and that only a proportion of these molecules actively participate in cell cycle regulation as part of MCM complexes. Using an improved method for constructing conditional degron mutants, Labib et al. (2000) demonstrated that depletion of minichromosome maintenance protein complexes after initiation irreversibly blocks the progression of replication forks in S. cerevisiae. Their experiments demonstrated that MCM complex is loaded at origins before initiation and is essential for elongation. Disruption of any one of the MCMs resulted in cells that were unable to complete the S phase, indicating that all MCM proteins are equally important for chromosome replication to continue after the activation of early origins of DNA replication. Labib et al. (2000) concluded that restricting MCM loading to the G1 phase ensures that initiation and elongation occur just once per cell cycle. The MCM2-7 complex is comprised of 6 subunits, MCM2 through MCM7, and is a ring-shaped heterohexameric ATPase involved in DNA replication. In Xenopus egg extracts, Pacek et al. (2006) showed that the MCM2-7 complex, the GINS complex (see GINS1; 610608), and Cdc45 (CDC45L; 603465) were enriched at stalled replication forks. They proposed that these components unwind DNA and separate DNA stra ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 116945 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).