Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Apr 30;10(5):331.
doi: 10.3390/genes10050331.

Post-Translational Modifications of the Mini-Chromosome Maintenance Proteins in DNA Replication

Zheng Li  1   2 , Xingzhi Xu  3
Affiliations
Review

Post-Translational Modifications of the Mini-Chromosome Maintenance Proteins in DNA Replication

Zheng Li et al. Genes (Basel). .

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.

Keywords: DNA replication; cancer; cell cycle; disease; genome stability; mini-chromosome maintenance (MCM); post-translational modifications (PTMs).

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Mini-chromosome maintenance (MCM) phosphorylation. ADP, adenosine diphosphate; ATP, adenosine triphosphate.
Figure 2
Figure 2
MCM ubiquitination.
Figure 3
Figure 3
MCM modification by the ubiquitin-fold modifier 1 (UFMylation).
Figure 4
Figure 4
MCM modification by small ubiquitin-like modifier (SUMOylation).
Figure 5
Figure 5
MCM O-N-acetyl-D-glucosamine (GlcNAc)ylation. OGT, O-GlcNAc transferase; OGA, O-GlcNAcase; UDP, uridine diphosphate.
Figure 6
Figure 6
MCM acetylation. KATs, lysine acetyltransferases; HDACs, histone deacetylases; SIRTs, nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase sirtuins.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Gaillard H., Garcia-Muse T., Aguilera A. Replication stress and cancer. Nat. Rev. Cancer. 2015;15:276–289. doi: 10.1038/nrc3916. - DOI - PubMed
    1. Masai H., You Z., Arai K. Control of DNA replication: Regulation and activation of eukaryotic replicative helicase, MCM. IUBMB Life. 2005;57:323–335. doi: 10.1080/15216540500092419. - DOI - PubMed
    1. Lujan S.A., Williams J.S., Kunkel T.A. DNA Polymerases Divide the Labor of Genome Replication. Trends Cell Biol. 2016;26:640–654. doi: 10.1016/j.tcb.2016.04.012. - DOI - PMC - PubMed
    1. Forment J.V., O’Connor M.J. Targeting the replication stress response in cancer. Pharmacol. Ther. 2018;188:155–167. doi: 10.1016/j.pharmthera.2018.03.005. - DOI - PubMed
    1. D’Angiolella V., Donato V., Forrester F.M., Jeong Y.T., Pellacani C., Kudo Y., Saraf A., Florens L., Washburn M.P., Pagano M. Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair. Cell. 2012;149:1023–1034. doi: 10.1016/j.cell.2012.03.043. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources