title: Msh2 deficiency leads to chromosomal abnormalities, centrosome amplification, and telomere capping defect.
abstract: Msh2 is a key mammalian DNA mismatch repair (MMR) gene and mutations or deficiencies in mammalian Msh2 gene result in microsatellite instability (MSI+) and the development of cancer. Here, we report that primary mouse embryonic fibroblasts (MEFs) deficient in the murine MMR gene Msh2 (Msh2(-/-)) showed a significant increase in chromosome aneuploidy, centrosome amplification, and defective mitotic spindle organization and unequal chromosome segregation. Although Msh2(-/-) mouse tissues or primary MEFs had no apparent change in telomerase activity, telomere length, or recombination at telomeres, Msh2(-/-) MEFs showed an increase in chromosome end-to-end fusions or chromosome ends without detectable telomeric DNA. These data suggest that MSH2 helps to maintain genomic stability through the regulation of the centrosome and normal telomere capping in vivo and that defects in MMR can contribute to oncogenesis through multiple pathways.
authors.affiliation: Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: M R
authors.initials: MR
authors.lastname: Campbell
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: S E
authors.initials: SE
authors.lastname: Andrew
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D018385:Centrosome; D002869:Chromosome Aberrations; D004260:DNA Repair; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005784:Gene Amplification; D051379:Mice; D018345:Mice, Knockout; D051718:MutS Homolog 2 Protein / Q000172:deficiency*; D016615:Telomere / Q000502:physiology*
chemical_list: C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein