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Mouse models of XRCC1 DNA repair polymorphisms and cancer

Abstract

DNA damage plays a major role in mutagenesis, carcinogenesis and aging. A gene that is emerging as an essential element in the repair of both damaged bases and single-strand breaks (SSB) is XRCC1. XRCC1 has been shown to have a large number of single-nucleotide polymorphisms (SNPs), several of which are being increasingly studied in cancer epidemiology investigations, in part because of their relative high frequency in the population. Although association trends with specific cancer types have occasionally been shown in a variety of ethnic backgrounds, there are often conflicting reports that weaken any substantial conclusions. The functional significance of these SNPs is still largely unknown. XRCC1 is an excellent prototype to provide a forum for determining how epidemiological cancer association studies with DNA repair gene polymorphisms can be validated or refuted. The focus is on the utilization of in silico data and biochemical studies in cell lines and existing mouse models to help provide a framework for the development of new mutant mouse lines that mimic human polymorphisms. These mouse lines will provide the next generation of mammalian tools for carcinogen exposure studies relevant to human cancer and variations in XRCC1, and provide the basis for investigating groups of genes and polymorphisms in an animal model.

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Acknowledgements

Studies were supported by NIEHS Grant U01 ES11045, (Ladiges PI), and NIEHS Grant P30 ES07033 (Eaton PI; Ladiges Core PI).

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Correspondence to W C Ladiges.

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Ladiges, W. Mouse models of XRCC1 DNA repair polymorphisms and cancer. Oncogene 25, 1612–1619 (2006). https://doi.org/10.1038/sj.onc.1209370

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  • DOI: https://doi.org/10.1038/sj.onc.1209370

Keywords

  • DNA repair
  • polymorphisms
  • XRCC1
  • cancer
  • mouse models

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