The assembly of the MCM2–7 hetero-hexamer and its significance in DNA replication

Abstract

The mini-chromosome maintenance proteins 2–7 (MCM2–7) hexamer is a protein complex that is key for eukaryotic DNA replication, which occurs only once per cell cycle. To achieve DNA replication, eukaryotic cells developed multiple mechanisms that control the timing of the loading of the hexamer onto chromatin and its activation as the replicative helicase. MCM2–7 is highly abundant in proliferating cells, which confers resistance to replication stress. Thus, the presence of an excess of MCM2–7 is important for maintaining genome integrity. However, the mechanism via which high MCM2–7 levels are achieved, other than the transcriptional upregulation of the MCM genes in the G1 phase, remained unknown. Recently, we and others reported that the MCM-binding protein (MCMBP) plays a role in the maintenance of high MCM2–7 levels and hypothesized that MCMBP functions as a chaperone in the assembly of the MCM2–7 hexamer. In this review, we discuss the roles of MCMBP in the control of MCM proteins and propose a model of the assembly of the MCM2–7 hexamer. Furthermore, we discuss a potential mechanism of the licensing checkpoint, which arrests the cells in the G1 phase when the levels of chromatin-bound MCM2–7 are reduced, and the possibility of targeting MCMBP as a chemotherapy for cancer.