Document Detail


DNA mismatch repair protein Msh6 is required for optimal levels of ultraviolet-B-induced apoptosis in primary mouse fibroblasts.
MedLine Citation:
PMID:  14632208     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent data support a role for DNA mismatch repair in the cellular response to some forms of exogenous DNA damage beyond that of DNA repair; cells with defective DNA mismatch repair have partial or complete failure to undergo apoptosis and/or G2M arrest following specific types of damage. We propose that the DNA mismatch repair Msh2/Msh6 heterodimer, responsible for the detection of DNA damage, promotes apoptosis in normal cells, thus protecting mammals from ultraviolet-induced malignant transformation. Using primary mouse embryonic fibroblasts derived from Msh6+/+ and Msh6-/- mice, we compare the response of DNA-mismatch repair-proficient and -deficient cells to ultraviolet B radiation. In the wild-type mouse embryonic fibroblasts, ultraviolet-B-induced increases in Msh6 protein levels were not dependent on p53. Msh6-/- mouse embryonic fibroblasts were significantly less sensitive to the cytotoxic effects of ultraviolet B radiation. Further comparison of the Msh6+/+ and Msh6-/- mouse embryonic fibroblasts revealed that Msh6-/- mouse embryonic fibroblasts undergo significantly less apoptosis following ultraviolet B irradiation, thus indicating that ultraviolet-B-induced apoptosis is partially Msh6 dependent. These data support a role for Msh6 in protective cellular responses of primary cells to ultraviolet-B-induced mutagenesis and, hence, the prevention of skin cancer.
Authors:
Leah C Young; Anthea C Peters; Tomoko Maeda; Winfried Edelmann; Raju Kucherlapati; Susan E Andrew; Victor A Tron
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  121     ISSN:  0022-202X     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-11-24     Completed Date:  2003-12-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  876-80     Citation Subset:  IM    
Affiliation:
Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / physiology*,  radiation effects
Cell Survival / physiology,  radiation effects
Cells, Cultured
DNA Repair / physiology*
DNA-Binding Proteins / genetics*,  metabolism*
Fibroblasts / cytology,  physiology*,  radiation effects
Mice
Mice, Knockout
Skin Neoplasms / prevention & control
Tumor Suppressor Protein p53 / genetics
Ultraviolet Rays / adverse effects
Grant Support
ID/Acronym/Agency:
CA76329/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/G-T mismatch-binding protein; 0/Msh6 protein, mouse; 0/Tumor Suppressor Protein p53

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