Abstract
The eukaryotic mini-chromosome maintenance (MCM) complex, composed of MCM proteins 2–7, is the core component of the replisome that acts as the DNA replicative helicase to unwind duplex DNA and initiate DNA replication. MCM10 tightly binds the cell division control protein 45 homolog (CDC45)/MCM2–7/ DNA replication complex Go-Ichi-Ni-San (GINS) (CMG) complex that stimulates CMG helicase activity. The MCM8–MCM9 complex may have a non-essential role in activating the pre-replicative complex in the gap 1 (G1) phase by recruiting cell division cycle 6 (CDC6) to the origin recognition complex (ORC). Each MCM subunit has a distinct function achieved by differential post-translational modifications (PTMs) in both DNA replication process and response to replication stress. Such PTMs include phosphorylation, ubiquitination, small ubiquitin-like modifier (SUMO)ylation, O-N-acetyl-D-glucosamine (GlcNAc)ylation, and acetylation. These PTMs have an important role in controlling replication progress and genome stability. Because MCM proteins are associated with various human diseases, they are regarded as potential targets for therapeutic development. In this review, we summarize the different PTMs of the MCM proteins, their involvement in DNA replication and disease development, and the potential therapeutic implications.
Highlights
DNA replication is a complex and systematic process that ensures faithful duplication of the genome and subsequent cell division only once per cell cycle
We summarize the different post-translational modifications (PTMs) of the mini-chromosome maintenance (MCM) proteins, their involvement in DNA replication and disease development, and the potential therapeutic implications
Both MCM8 and MCM9 in Xenopus egg extracts bind with chromatin in late S phase, depletion of both has no impact on MCM2–7 complex loading, but reduces the chromatin-bound cell division control protein 45 (CDC45) and GINS2 levels [18]
Summary
DNA replication is a complex and systematic process that ensures faithful duplication of the genome and subsequent cell division only once per cell cycle. In early gap 1 (G1) phase, the ORC recruits the DNA replication licensing factor cell division cycle. 6 (CDC6) and chromatin licensing and DNA replication factor 1 (CDT1) to the replication origins, and this recruitment subsequently promotes loading of the mini-chromosome maintenance (MCM). CDC6 and CDT1 are released from the chromatin to prevent MCM2–7 reloading in the synthesis (S) phase and replication occurring more than once per cell cycle. During fork stalling, the nearby dormant MCM2–7 complex becomes activated to ensure replication. Fork stalling activates the DNA replication checkpoint, which mostly depends on the ataxia telangiectasia and Rad3-related (ATR)–checkpoint kinase-1(CHK1) pathway. We summarize the PTMs of the MCM family members, their involvement in DNA replication and associated human diseases, and the potential therapeutic implications
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
