Assembly of the Cdc45-MCM2-7-GINS Complex, the Replication Helicase

In eukaryotes, a crucial step during the initiation of DNA replication is the timely formation and activation of the replicative DNA helicase composed of Cdc45, MCM2-7 and GINS (CMG). The dynamic and spatio-temporal events leading to the ordered and stepwise assembly of the CMG helicase are tightly regulated. Multiple assembly factors ensure in this way that replication occurs only once per cell cycle. The MCM2-7 helicase is loaded in an inactive form onto double-stranded DNA in the G1 phase of the cell cycle, whereas the fully reconstituted CMG complex is assembled and positioned onto single-stranded DNA during the S phase. Thus, DNA plays an important and active role in these events. In this chapter we summarize and discuss our current knowledge about the appropriate recruitment and assembly of the CMG complex into the active eukaryotic replicative DNA helicase, emphasizing the crucial role of DNA in this process. We finally outline how the number of active CMG complexes formed is restricted during unperturbed DNA synthesis.