Mcm4:Mcm6:Mcm7 Mcm2-7 complex Rearrangement and mobilization of Mcm2-7 At the start of the elongation phase of DNA replication, the Mcm2-7 complex may re-arrange to function as the replicative helicase associated with the replication fork. In general, a replicative helicase is associated with the replication fork and unwinds DNA ahead of the polymerase. In yeast, the Mcm proteins associate with origin DNA in G1 phase and then exit the origin upon replication initiation, consistent with moving out of the origin with the replication fork. The Mcm2-7 complex is a ring-shaped hexamer. Complexes of Mcm4, Mcm6 and Mcm7 proteins from humans or S. pombe display a modest ATP-dependent helicase activity in vitro. Consistent with the hypothesis that eukaryotic Mcm complexes function as helicases, an archaeal Mcm homolog is a ring-shaped double hexamer that has a processive DNA unwinding activity. Mcm proteins may have additional functions during elongation, as uninterrupted function of all six is required for replication fork progression in budding yeast. Mcm4,6,7 helicase activity may be negatively regulated in two ways. Mcm2, Mcm4, Mcm6, and Mcm7 also form a stable complex which, however, has no helicase activity, suggesting that Mcm2 inhibits DNA unwinding by Mcm4,6,7. In addition, phosphorylation of human Mcm4,6,7 complex by CDK inhibits its helicase activity. Mcm4,6,7 trimer forms and associates with the replication fork Pubmed10567526 Pubmed10611290 Pubmed10677495 Pubmed10748114 Pubmed10834843 Pubmed10872463 Pubmed10884341 Pubmed11282021 Pubmed11454864 Pubmed12364596 Pubmed9305914 Pubmed9335335 Reactome Database ID Release 4369019 Reactome, http://www.reactome.org ReactomeREACT_1303