| Abstract: |
The hetero-hexameric Mcm2-7 complex is a multifunctional ATPase that plays essential roles during the initiation of DNA replication in eukaryotic cells. Initially, the Mcm2-7 complex is bound as a catalytically inactive double hexamer around double-stranded DNA, marking potential replication origin sites along the chromosome. Subsequently, upon activation, the Mcm2-7 complex mediates the opening, or “melting," of the parental DNA duplex at the origin, which culminates in the formation of two oppositely oriented DNA replication forks. Eventually, at the fork, the Mcm2-7 complex acts as the catalytic core of the replicative DNA helicase. In addition to unwinding DNA at the fork, the Mcm2-7 helicase complex also serves as the central scaffold around which the replisome is assembled. Due to its varied and essential roles in the initiation of DNA replication, the Mcm2-7 complex is a key target for regulatory mechanisms that govern origin activity in the cell cycle. Activation of the Mcm2-7 helicase entails a large conformational reconfiguration that results in the separation of the Mcm2-7 double hexamer into two individual Mcm2-7 hexamer complexes bound around the single-stranded leading strand template. Recent progress in the structural characterization of the Mcm2-7 complex begins to shed light on the mechanism by which origin unwinding is coupled to Mcm2-7 remodeling. © 2016 Springer International Publishing Switzerland. |
