Additive roles of XPA and MSH2 genes in UVB-induced skin tumorigenesis in mice

Masafumi Yoshino, Yoshimichi Nakatsu, Hein te Riele, Seiichi Hirota, Yukihiko Kitamura, Kiyoji Tanaka

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

We have made xeroderma pigmentosum group A gene (XPA)-knockout mice (XPA-/- mice). The XPA-/- mice had no detectable activity for nucleotide excision repair (NER) and showed a high incidence of UVB-induced skin tumorigenesis. We have also found that cell lines derived from skin cancers in UVB-irradiated XPA-/- mice become tolerant to UV-irradiation and showed abnormal UV-induced cell cycle checkpoints and decreased mismatch repair (MMR) activity. These results suggested that the MMR-downregulation may help cells escape killing by UV-irradiation and thus MMR-deficient clones are selected for during the tumorigenic transformation of XPA-/- cells. In this report, we examined whether the incidence of UVB-induced skin tumorigenesis is enhanced in XPA-/-MSH2-/-, XPA-/- and MSH2-/- mice when compared with that in wild-type mice. Our results indicate that the MSH2-deficiency caused a high incidence of spontaneous and UVB-induced skin tumorigenesis and the XPA and MSH2 genes have additive roles in the UV-induced skin tumorigenesis.

Original languageEnglish
Pages (from-to)935-940
Number of pages6
JournalDNA Repair
Volume1
Issue number11
DOIs
Publication statusPublished - Nov 1 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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