title: Mammalian DNA mismatch repair protects cells from UVB-induced DNA damage by facilitating apoptosis and p53 activation.
abstract: DNA mismatch repair (MMR) is integral to the maintenance of genomic stability and more recently has been demonstrated to affect apoptosis and cell cycle arrest in response to a variety of adducts induced by exogenous agents. Comparing Msh2-null and wildtype mouse embryonic fibroblasts (MEFs), both primary and transformed, we show that Msh2 deficiency results in increased survival post-UVB, and that UVB-induced apoptosis is significantly reduced in Msh2-deficient cells. Furthermore, p53 phosphorylation at serine 15 is delayed or diminished in Msh2-deficient cells, suggesting that Msh2 may act upstream of p53 in a post-UVB apoptosis or growth arrest response pathway. Taken together, these data suggest that MMR heterodimers containing Msh2 may function as a sensor of UVB-induced DNA damage and influence the initiation of UVB-induced apoptosis, thus implicating MMR in protecting against UV-induced tumorigenesis.
authors.affiliation: Department of Medical Genetics, University of Alberta, 8-33 Medical Sciences Building, Edmonton, Canada T6G 2H7.
authors.forename: Anthea C
authors.initials: AC
authors.lastname: Peters
authors.forename: Leah C
authors.initials: LC
authors.lastname: Young
authors.forename: Tomoko
authors.initials: T
authors.lastname: Maeda
authors.forename: Victor A
authors.initials: VA
authors.lastname: Tron
authors.forename: Susan E
authors.initials: SE
authors.lastname: Andrew
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair; D004268:DNA-Binding Proteins; D051379:Mice; D051718:MutS Homolog 2 Protein; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein