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

doi:10.1038/sj.onc.1203844

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 journal › Article › peer-review

53 Scopus citations

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 language	English (US)
Pages (from-to)	5034-5037
Number of pages	4
Journal	Oncogene
Volume	19
Issue number	43
DOIs	https://doi.org/10.1038/sj.onc.1203844
State	Published - Oct 12 2000

Keywords

Cancer
Hprt
Mutation
Nucleotide excision repair
Transgenic mice

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

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10.1038/sj.onc.1203844

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title = "Age-dependent spontaneous mutagenesis in Xpc mice defective in nucleotide excision repair",

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.",

keywords = "Cancer, Hprt, Mutation, Nucleotide excision repair, Transgenic mice",

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

note = "Funding Information: We thank C van Teijlingen for technical assistance on the isolation and culturing of splenic T-lymphocytes and selection of Hprt mutants and Dr T Jacks, MIT, for providing us with the p53+/7mice (Jacks et al., 1994). This work was financially supported by the Dutch Cancer Society (Project 96-1321).",

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doi = "10.1038/sj.onc.1203844",

language = "English (US)",

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AU - Wijnhoven, Susan W P

AU - Kool, Hanneke J M

AU - Mullenders, Leon H F

AU - Van Zeeland, Albert A.

AU - Friedberg, Errol C.

AU - Van Der Horst, Gijsbertus T J

AU - Van Steeg, Harry

AU - Vrieling, Harry

N1 - Funding Information: We thank C van Teijlingen for technical assistance on the isolation and culturing of splenic T-lymphocytes and selection of Hprt mutants and Dr T Jacks, MIT, for providing us with the p53+/7mice (Jacks et al., 1994). This work was financially supported by the Dutch Cancer Society (Project 96-1321).

PY - 2000/10/12

Y1 - 2000/10/12

N2 - 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.

AB - 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.

KW - Cancer

KW - Hprt

KW - Mutation

KW - Nucleotide excision repair

KW - Transgenic mice

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

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Keywords

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