Age-dependent spontaneous mutagenesis in Xpc mice defective in nucleotide excision repair

Susan W P Wijnhoven, Hanneke J M Kool, Leon H F Mullenders, Albert A. Van Zeeland, Errol C. Friedberg, Gijsbertus T J Van Der Horst, Harry Van Steeg, Harry Vrieling

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

DNA damages caused by cellular metabolites and environmental agents induce mutations, that may predispose to cancer. Nucleotide excision repair (NER) is a major cellular defence mechanism acting on a variety of DNA lesions. Here, we show that spontaneous mutant frequencies at the Hprt gene increased 30-fold in T-lymphocytes of 1 year old Xpc(-/-) mice, possessing only functional transcription-coupled repair (TCR). Hprt mutant frequencies in Xpa(-/-) and Csb(-/-) mice that both have a defect in this NER subpathway, remained low during ageing. In contrast to current models, the elevated mutation rate in Xpc(-/-) mice does not lead to an increased tumour incidence or premature ageing.

Original languageEnglish (US)
Pages (from-to)5034-5037
Number of pages4
JournalOncogene
Volume19
Issue number43
StatePublished - Oct 12 2000

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Mutagenesis
DNA Repair
Premature Aging
Mutation Rate
DNA Damage
Neoplasms
T-Lymphocytes
Mutation
DNA
Incidence
Genes

Keywords

  • Cancer
  • Hprt
  • Mutation
  • Nucleotide excision repair
  • Transgenic mice

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Wijnhoven, S. W. P., Kool, H. J. M., Mullenders, L. H. F., Van Zeeland, A. A., Friedberg, E. C., Van Der Horst, G. T. J., ... Vrieling, H. (2000). Age-dependent spontaneous mutagenesis in Xpc mice defective in nucleotide excision repair. Oncogene, 19(43), 5034-5037.

Age-dependent spontaneous mutagenesis in Xpc mice defective in nucleotide excision repair. / Wijnhoven, Susan W P; Kool, Hanneke J M; Mullenders, Leon H F; Van Zeeland, Albert A.; Friedberg, Errol C.; Van Der Horst, Gijsbertus T J; Van Steeg, Harry; Vrieling, Harry.

In: Oncogene, Vol. 19, No. 43, 12.10.2000, p. 5034-5037.

Research output: Contribution to journalArticle

Wijnhoven, SWP, Kool, HJM, Mullenders, LHF, Van Zeeland, AA, Friedberg, EC, Van Der Horst, GTJ, Van Steeg, H & Vrieling, H 2000, 'Age-dependent spontaneous mutagenesis in Xpc mice defective in nucleotide excision repair', Oncogene, vol. 19, no. 43, pp. 5034-5037.
Wijnhoven SWP, Kool HJM, Mullenders LHF, Van Zeeland AA, Friedberg EC, Van Der Horst GTJ et al. Age-dependent spontaneous mutagenesis in Xpc mice defective in nucleotide excision repair. Oncogene. 2000 Oct 12;19(43):5034-5037.
Wijnhoven, Susan W P ; Kool, Hanneke J M ; Mullenders, Leon H F ; Van Zeeland, Albert A. ; Friedberg, Errol C. ; Van Der Horst, Gijsbertus T J ; Van Steeg, Harry ; Vrieling, Harry. / Age-dependent spontaneous mutagenesis in Xpc mice defective in nucleotide excision repair. In: Oncogene. 2000 ; Vol. 19, No. 43. pp. 5034-5037.
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