» Articles » PMID: 19946136

The Mcm Complex: Unwinding the Mechanism of a Replicative Helicase

Overview
Specialty Microbiology
Date 2009 Dec 1
PMID 19946136
Citations 183
Authors
Affiliations
Soon will be listed here.
Abstract

The Mcm2-7 complex serves as the eukaryotic replicative helicase, the molecular motor that both unwinds duplex DNA and powers fork progression during DNA replication. Consistent with its central role in this process, much prior work has illustrated that Mcm2-7 loading and activation are landmark events in the regulation of DNA replication. Unlike any other hexameric helicase, Mcm2-7 is composed of six unique and essential subunits. Although the unusual oligomeric nature of this complex has long hampered biochemical investigations, recent advances with both the eukaryotic as well as the simpler archaeal Mcm complexes provide mechanistic insight into their function. In contrast to better-studied homohexameric helicases, evidence suggests that the six Mcm2-7 complex ATPase active sites are functionally distinct and are likely specialized to accommodate the regulatory constraints of the eukaryotic process.

Citing Articles

Novel De Novo Variant in an Early-Onset Ovarian Cancer Reveals a Unique Tumor Evolution Pathway.

Miolo G, Canil G, Polano M, Dal Bo M, Mondello A, Palumbo A Int J Mol Sci. 2025; 26(5).

PMID: 40076915 PMC: 11899998. DOI: 10.3390/ijms26052295.


Increased levels of lagging strand polymerase α in an adult stem cell lineage affect replication-coupled histone incorporation.

Davis B, Snedeker J, Ranjan R, Wooten M, Barton S, Blundon J Sci Adv. 2025; 11(9):eadu6799.

PMID: 40020063 PMC: 11870066. DOI: 10.1126/sciadv.adu6799.


A Step Toward Understanding Direct Impacts of a Higher Estrus-Associated Temperature (HEAT): Transcript Level Changes in Cumulus-Oocyte Complexes Directly Exposed to Acute Elevated Temperature.

Klabnik J, Beever J, Payton R, Lamour K, Schrick F, Edwards J Animals (Basel). 2025; 15(4).

PMID: 40003000 PMC: 11851612. DOI: 10.3390/ani15040517.


The Shu complex interacts with the replicative helicase to prevent mutations and aberrant recombination.

Fagunloye A, De Magis A, Little J, Contreras I, Dorwart T, Bonilla B EMBO J. 2025; 44(5):1512-1539.

PMID: 39838174 PMC: 11876325. DOI: 10.1038/s44318-025-00365-9.


Minichromosome Maintenance Proteins: From DNA Replication to the DNA Damage Response.

Malysa A, Zhang X, Bepler G Cells. 2025; 14(1.

PMID: 39791713 PMC: 11719910. DOI: 10.3390/cells14010012.


References
1.
Seki T, Diffley J . Stepwise assembly of initiation proteins at budding yeast replication origins in vitro. Proc Natl Acad Sci U S A. 2000; 97(26):14115-20. PMC: 18880. DOI: 10.1073/pnas.97.26.14115. View

2.
Li D, Zhao R, Lilyestrom W, Gai D, Zhang R, DeCaprio J . Structure of the replicative helicase of the oncoprotein SV40 large tumour antigen. Nature. 2003; 423(6939):512-8. DOI: 10.1038/nature01691. View

3.
Ibarra A, Schwob E, Mendez J . Excess MCM proteins protect human cells from replicative stress by licensing backup origins of replication. Proc Natl Acad Sci U S A. 2008; 105(26):8956-61. PMC: 2449346. DOI: 10.1073/pnas.0803978105. View

4.
Aparicio O, Stout A, Bell S . Differential assembly of Cdc45p and DNA polymerases at early and late origins of DNA replication. Proc Natl Acad Sci U S A. 1999; 96(16):9130-5. PMC: 17744. DOI: 10.1073/pnas.96.16.9130. View

5.
Liku M, Nguyen V, Rosales A, Irie K, Li J . CDK phosphorylation of a novel NLS-NES module distributed between two subunits of the Mcm2-7 complex prevents chromosomal rereplication. Mol Biol Cell. 2005; 16(10):5026-39. PMC: 1237101. DOI: 10.1091/mbc.e05-05-0412. View