Mammalian DNA mismatch repair protects cells from UVB-induced DNA damage by facilitating apoptosis and p53 activation.
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.
Peters
Anthea C
AC
Department of Medical Genetics, University of Alberta, 8-33 Medical Sciences Building, Edmonton, Canada T6G 2H7.
Young
Leah C
LC
Maeda
Tomoko
T
Tron
Victor A
VA
Andrew
Susan E
SE
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
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein