MCM27Helikasekomplex

The MCM2-7 helicase complex, also called the MCM2-7 hexamer, is a conserved eukaryotic protein assembly essential for DNA replication. It comprises six related AAA+ ATPases—MCM2, MCM3, MCM4, MCM5, MCM6 and MCM7—that come together to form a hexameric ring capable of encircling DNA and providing the helicase activity required at replication forks.

In late M or early G1 phase, replication origins are licensed by the origin recognition complex (ORC) together with Cdc6 and Cdt1, which load the MCM2-7 complex onto DNA as an inactive double hexamer. This licensing ensures origins are prepared for replication but prevents firing more than once per cell cycle.

Entry into S phase triggers activation of the complex, primarily through phosphorylation by CDKs and DDK (Dbf4-dependent kinase) and the recruitment of Cdc45 and the GINS complex to form the active CMG helicase (Cdc45-MCM-GINS). The CMG complex unwinds duplex DNA ahead of the replication machinery, enabling synthesis by DNA polymerases on both the leading and lagging strands.

Regulation of MCM2-7 loading and activation is crucial for genome stability. Inappropriate licensing or activation can lead to rereplication, replication stress, or incomplete replication. Altered expression or function of MCM proteins has been associated with various cancers and remains an active area of research.

Evolutionarily, MCM genes are highly conserved in eukaryotes, with archaeal MCMs sharing structural and functional similarities. The discovery of the MCM family arose from studies of replicative helicases in yeast and other organisms in the late 20th century.