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

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

S W Wijnhoven  1 , H J Kool, L H Mullenders, A A van Zeeland, E C Friedberg, G T van der Horst, H van Steeg, H Vrieling
Affiliations

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

S W Wijnhoven et al. Oncogene. .

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. Oncogene (2000) 19, 5034 - 5037

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