DNA Mismatch Repair Protein Msh6 Is Required for Optimal Levels of Ultraviolet-B-Induced Apoptosis in Primary Mouse Fibroblasts

Leah C. Young, Anthea C. Peters, Tomoko Maeda, Winfried Edelmann, Raju Kucherlapati, Susan E. Andrew, Victor A. Tron

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)876-880
Number of pages5
JournalJournal of Investigative Dermatology
Volume121
Issue number4
DOIs
StatePublished - Oct 1 2003

Keywords

  • Apoptosis
  • Cytotoxicity
  • DNA mismatch repair
  • Msh6
  • Ultraviolet B

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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