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Updated: Jan 29, 2026

Single-Molecule Real-Time Visualization of DNA Unwinding by CMG Helicase
Published on: September 27, 2024
The MCM8/9 complex: A recent recruit to the roster of helicases involved in genome maintenance
Wezley C Griffin1, Michael A Trakselis1
1Department of Chemistry and Biochemistry, Baylor University, Waco, Texas, 76798, USA.
Abstract:
There are several DNA helicases involved in seemingly overlapping aspects of homologous and homoeologous recombination. Mutations of many of these helicases are directly implicated in genetic diseases including cancer, rapid aging, and infertility. MCM8/9 are recent additions to the catalog of helicases involved in recombination, and so far, the evidence is sparse, making assignment of function difficult. Mutations in MCM8/9 correlate principally with primary ovarian failure/insufficiency (POF/POI) and infertility indicating a meiotic defect. However, they also act when replication forks collapse/break shuttling products into mitotic recombination and several mutations are found in various somatic cancers. This review puts MCM8/9 in context with other replication and recombination helicases to narrow down its genomic maintenance role. We discuss the known structure/function relationship, the mutational spectrum, and dissect the available cellular and organismal data to better define its role in recombination.
Insights
The MCM8/9 helicase plays a role in DNA repair and recombination, impacting fertility and cancer. Further research is needed to fully understand its genomic maintenance functions.
Area of Science:
- Genetics
- Molecular Biology
- Genomic Maintenance
Background:
- Multiple DNA helicases are involved in homologous and homoeologous recombination.
- Mutations in these helicases are linked to genetic diseases like cancer, aging, and infertility.
- MCM8/9 helicases are newly identified players in recombination with limited functional data.
Purpose of the Study:
- To clarify the genomic maintenance role of MCM8/9 helicases.
- To contextualize MCM8/9 within other replication and recombination helicases.
- To define the function of MCM8/9 by analyzing its structure, mutations, and cellular/organismal data.
Main Methods:
- Literature review and data synthesis.
- Analysis of structure-function relationships.
- Examination of mutational spectrum and available cellular/organismal data.
Main Results:
- MCM8/9 mutations are primarily associated with primary ovarian insufficiency and infertility, suggesting a meiotic role.
- MCM8/9 also functions in mitotic recombination following replication fork collapse.
- MCM8/9 mutations are found in various somatic cancers.
Conclusions:
- MCM8/9 helicases are involved in both meiotic and mitotic DNA recombination.
- Their dysfunction contributes to infertility and cancer development.
- Further investigation is crucial to fully elucidate the precise genomic maintenance functions of MCM8/9.
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