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Published on: August 15, 2019
Functional screen of human MCM2-7 variant alleles for disease-causing potential
Nathan A Steere1, Satoru Yamaguchi, Catherine A Andrews
1Department of Genetics, Cell Biology and Development, College of Biological Sciences,Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, United States.
Mutation Research
|June 2, 2009
Summary
Minichromosome maintenance (MCM2-7) proteins are crucial for DNA replication and genome stability. A study identified a variant MCM5 gene allele with pathogenic potential, suggesting a link to cancer susceptibility in humans.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Origin licensing is fundamental for genome stability during DNA replication.
- Deregulation of origin licensing and the MCM2-7 complex are linked to replication stress and cancer.
- Previous studies in mice show Mcm mutant alleles cause genome instability and tumors.
Purpose of the Study:
- To investigate the cancer-causing potential of human MCM2-7 gene variants.
- To circumvent the essential nature of MCM2-7 genes by studying single nucleotide polymorphisms (SNPs).
- To screen for variant alleles with pathogenic potential using a yeast model.
Main Methods:
- Created 14 variant alleles of human MCM2-7 genes in Saccharomyces cerevisiae.
- Assayed phenotypic consequences, including minichromosome loss, as a surrogate for genome instability.
- Utilized minichromosome loss as a proxy for cancer susceptibility.
Main Results:
- Identified a specific MCM5 variant allele exhibiting pathogenic potential.
- Demonstrated that this MCM5 variant can lead to genome instability in yeast.
- The findings suggest a potential role in human cancer development.
Conclusions:
- Variant MCM genes, particularly MCM5, may contribute to human cancer susceptibility.
- Further investigation of the identified MCM5 variant in human populations is warranted.
- This research provides a novel approach to study essential genes in cancer development.
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