Pathways & interactions
Mini-chromosome maintenance protein (IPR031327)
Short name: MCM
Overlapping homologous superfamilies
- Mini-chromosome maintenance protein (IPR031327)
- DNA replication licensing factor Mcm (IPR008048)
- DNA replication licensing factor Mcm2 (IPR008045)
- DNA replication licensing factor Mcm3 (IPR008046)
- DNA replication licensing factor Mcm6 (IPR008049)
- DNA replication licensing factor Mcm7 (IPR008050)
- Mini-chromosome maintenance complex protein 4 (IPR008047)
MCM proteins are DNA-dependent ATPases required for the initiation of eukaryotic DNA replication [PMID: 1454522, PMID: 8265339, PMID: 14731643]. In eukaryotes there is a family of six proteins, MCM2 to MCM7. They were first identified in yeast where most of them have a direct role in the initiation of chromosomal DNA replication by interacting directly with autonomously replicating sequences (ARS). They were thus called minichromosome maintenance proteins, MCM proteins [PMID: 8332451].
This family is also present in the archebacteria in 1 to 4 copies. Methanocaldococcus jannaschii (Methanococcus jannaschii) has four members, MJ0363, MJ0961, MJ1489 and MJECL13.
The "MCM motif" contains Walker-A and Walker-B type nucleotide binding motifs. The diagnostic sequence defining the MCMs is IDEFDKM. Only Mcm2 (aka Cdc19 or Nda1) has been subjected to mutational analysis in this region, and most mutations abolish its activity [PMID: 9383050]. The presence of a putative ATP-binding domain implies that these proteins may be involved in an ATP-consuming step in the initiation of DNA replication in eukaryotes.
The MCM proteins bind together in a large complex [PMID: 9366552]. Within this complex, individual subunits associate with different affinities, and there is a tightly associated core of Mcm4 (Cdc21), Mcm6 (Mis5) and Mcm7 [PMID: 9658174]. This core complex in human MCMs has been associated with helicase activity in vitro [PMID: 9305914], leading to the suggestion that the MCM proteins are the eukaryotic replicative helicase.
Schizosaccharomyces pombe (Fission yeast) MCMs, like those in metazoans, are found in the nucleus throughout the cell cycle. This is in contrast to the Saccharomyces cerevisiae (Baker's yeast) in which MCM proteins move in and out of the nucleus during each cell cycle. The assembly of the MCM complex in S. pombe is required for MCM localisation, ensuring that only intact MCM complexes remain in the nucleus [PMID: 10588642].