Structure and Activity of the Cdc45-Mcm2–7-GINS (CMG) Complex, the Replication Helicase

Highly efficient unwinding of double-stranded DNA is an essential prerequisite for duplication of the genetic material. In eukaryotes this process is catalysed by the CMG (Cdc45-Mcm2–7-GINS) complex, which is composed by 11 proteins: the Cdc45 replication factor, the hetero-hexameric Mcm2–7 and the tetrameric GINS complex. Although the Mcm2–7 is the helicase motor, in the absence of the other components the purified Mcm complex displays only a weak and labile helicase activity; in contrast, a stable complex comprising Cdc45, Mcm2–7 and GINS can be co-expressed and/or reconstituted, and shows a robust helicase activity.