期刊
GENES
卷 10, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/genes10050331
关键词
mini-chromosome maintenance (MCM); post-translational modifications (PTMs); disease; cancer; DNA replication; cell cycle; genome stability
资金
- National Natural Science Foundation of China (NSFC) [31761133012, 31530016]
- Shenzhen Science and Technology Innovation Commission [JCYJ20170412113009742, JCYJ20180507182213033]
- China Postdoctoral Science Foundation [2018M633143]
- 973 projects [2017YFA0503900, 2015CB910601]
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.
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