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.
Similar content being viewed by others
References
Aka P, Mateuca R, Buchet JP, Thierens H, Kirsch-Volders M . (2004). Mutat Res 556 (1–2): 169–181.
Au WW, Salama SA, Sierra-Torres CH . (2003). Environ Health Perspect 111 (15): 1843–1850.
Beernink PT, Hwang M, Ramirez M, Murphy MB, Doyle SA, Thelen MP . (2005). J Biol Chem 280 (34): 30206–30213.
Brem R, Hall J . (2005). Nucleic Acids Res 33 (8): 2512–2520.
Caldecott KW . (2003). DNA Repair (Amst) 2 (9): 955–969.
De Bont R, van Larebeke N . (2004). Mutagenesis 19 (3): 169–185.
Dianova II, Sleeth KM, Allinson SL, Parsons JL, Breslin C, Caldecott KW et al. (2004). Nucleic Acids Res 32 (8): 2550–2555.
El-Khamisy SF, Masutani M, Suzuki H, Caldecott KW . (2003). Nucleic Acids Res 31 (19): 5526–5533.
Fan J, Otterlei M, Wong HK, Tomkinson AE, Wilson III DM . (2004). Nucleic Acids Res 32 (7): 2193–2201.
Geisler SA, Olshan AF, Cai J, Weissler M, Smith J, Bell D . (2005). Head Neck 27 (3): 232–242.
Goode EL, Ulrich CM, Potter JD . (2002). Epidemiol Biomarkers Prev 11 (12): 1513–1530.
Hu Z, Ma H, Chen F, Wei Q, Shen H . (2005). Cancer Epidemiol Biomarkers Prev 14 (7): 1810–1818.
Hung RJ, Brennan P, Canzian F, Szeszenia-Dabrowska N, Zaridze D, Lissowska J et al. (2005). Natl Cancer Inst 97 (8): 567–576.
Kelada SN, Eaton DL, Wang SS, Rothman NR, Khoury MJ . (2003). Environ Health Perspect 111 (8): 1055–1064.
Kirk GD, Turner PC, Gong Y, Lesi OA, Mendy M, Goedert JJ et al. (2005). Cancer Epidemiol Biomarkers Prev 14 (2): 373–379.
Loizou JI, El-Khamisy SF, Zlatanou A, Moore DJ, Chan DW, Qin J et al. (2004). Cell 117 (1): 17–28.
Marintchev A, Mullen MA, Maciejewski MW, Pan B, Gryk MR, Mullen GP . (1999). Nat Struct Biol 6 (9): 884–893.
Marsin S, Vidal AE, Sossou M, Menissier-de Murcia J, Le Page F, Boiteux S et al. (2003). J Biol Chem 278 (45): 44068–44074.
Moullan N, Cox DG, Angele S, Romestaing P, Gerard JP, Hall J . (2003). Cancer Epidemiol Biomarkers Prev 12 (11 Part 1): 1168–1174.
Ron E . (1998). Radiat Res 150 (5 Suppl): S30–41.
Shen MR, Zdzienicka MZ, Mohrenweiser H, Thompson LH, Thelen MP . (1998). Nucleic Acids Res 26 (4): 1032–1037.
Takanami T, Nakamura J, Kubota Y, Horiuchi S . (2005). Mutat Res 582 (1–2): 135–145.
Taylor RM, Thistlethwaite A, Caldecott KW . (2002). Mol Cell Biol 22 (8): 2556–2563.
Tebbs RS, Flannery ML, Meneses JJ, Hartmann A, Tucker JD, Thompson LH et al. (1999). Dev Biol 208 (2): 513–529.
Tebbs RS, Thompson LH, Cleaver JE . (2003). DNA Repair (Amst) 2 (12): 1405–1417.
Thompson LH, West MG . (2000). Mutat Res 459 (1): 1–18.
Wallace SS . (1994). Int J Radiat Biol 66 (5): 579–589.
Wang Y, Spitz MR, Zhu Y, Dong Q, Shete S, Wu X . (2003). DNA Repair (Amst) 2 (8): 901–908.
Zhang X, Morera S, Bates PA, Whitehead PC, Coffer AI, Hainbucher K et al. (1998). EMBO J 17 (21): 6404–6411.
Acknowledgements
Studies were supported by NIEHS Grant U01 ES11045, (Ladiges PI), and NIEHS Grant P30 ES07033 (Eaton PI; Ladiges Core PI).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ladiges, W. Mouse models of XRCC1 DNA repair polymorphisms and cancer. Oncogene 25, 1612–1619 (2006). https://doi.org/10.1038/sj.onc.1209370
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1209370
- Springer Nature Limited
Keywords
This article is cited by
-
Elucidation of Increased Cervical Cancer Risk Due to Polymorphisms in XRCC1 (R399Q and R194W), ERCC5 (D1104H), and NQO1 (P187S)
Reproductive Sciences (2023)
-
Promoter CpG island hypermethylation and down regulation of XRCC1 gene can augment in the gastric carcinogenesis events
Molecular Biology Reports (2021)
-
DNA repair genes hOGG1, XRCC1 and ERCC2 polymorphisms and their molecular mapping in breast cancer patients from India
Molecular Biology Reports (2020)
-
Proteomics in Inflammatory Bowel Disease: Approach Using Animal Models
Digestive Diseases and Sciences (2017)
-
New paradigms in the repair of oxidative damage in human genome: mechanisms ensuring repair of mutagenic base lesions during replication and involvement of accessory proteins
Cellular and Molecular Life Sciences (2015)