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

Oncogene. 2000 Oct 12;19(43):5034-7. doi: 10.1038/sj.onc.1203844.


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. Oncogene (2000) 19, 5034 - 5037

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Animals
  • DNA Repair / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Hypoxanthine Phosphoribosyltransferase / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Mutagenesis*
  • Neoplasms, Experimental / genetics
  • Spleen / cytology
  • T-Lymphocytes / physiology
  • Transcription, Genetic / genetics
  • Xeroderma Pigmentosum / genetics*


  • Hypoxanthine Phosphoribosyltransferase