MCM proteins are DNA-dependent ATPases required for the initiation of eukaryotic DNA replication [, , ]. In eukaryotes there is a family of eight proteins, MCM2 to MCM9. They were first identified in yeast where most of them have adirect 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 []. These proteins are evolutionarily related and belong to the AAA+ superfamily. They contain the Mcm family domain, which includes motifs that are required for ATP hydrolysis (such as the Walker A and B, and R-finger motifs). Mcm2-7 forms a hexameric complex []in which individual subunits associate with different affinities, and there is a tightly associated core of Mcm4 (Cdc21), Mcm6 (Mis5) and Mcm7 []. Mcm2-7 complex is the replicative helicase involved in replication initiation and elongation [], whereas Mcm8 and Mcm9 from and separate one, conserved among many eukaryotes except yeast and C. elegans. Mcm8/9 complex play a role during replication elongation or recombination, being involved in the repair of double-stranded DNA breaks and DNA interstrand cross-links by homologous recombination. Drosophila is the only organism that has MCM8 without MCM9, involved in meiotic recombination [, ].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.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 [].
Proteins shown to be required for the initiation of eukaryotic DNA replication share a highly conserved domain of about 210 amino-acid residues [, , ]. The latter shows some similarities []with that of various other families of DNA-dependent ATPases. Eukaryotes seem to possess a family of eight proteins that contain this domain. 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' with gene symbols prefixedby MCM. These six proteins are:MCM2, also known as cdc19 (in S.pombe).MCM3, also known as DNA polymerase alphaholoenzyme-associated protein P1,RLF beta subunit or ROA.MCM4, also known as CDC54, cdc21 (in S.pombe) or dpa (in Drosophila).MCM5, also known as CDC46 or nda4 (in S.pombe).MCM6, also known as mis5 (in S.pombe).MCM7, also known as CDC47 or Prolifera (in A.thaliana).MCM8, also known as as REC (in Drosophila).MCMThese proteins are evolutionarily related and belong to the AAA+ superfamily. They contain the Mcm family domain, which includes motifs that are required for ATP hydrolysis (such as the Walker A and B, and R-finger motifs). Mcm2-7 forms a hexameric complex which is the replicative helicase involved in replication initiation and elongation, whereas Mcm8 and Mcm9 from and separate one, conserved among many eukaryotes except yeast and C. elegans. Mcm8/9 complex play a role during replication elongation or recombination, being involved in the repair of double-stranded DNA breaks and DNA interstrand cross-links by homologous recombination. Drosophila is the only organism that has MCM8 without MCM9, involved in meiotic recombination [, ].
