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Science 291 (5507): 1284-1289
Copyright © 2001 by the American Association for the Advancement of Science
Human DNA Repair Genes
Richard D. Wood,1*
Michael Mitchell,2
John Sgouros,2
Tomas Lindahl1
Cellular DNA is subjected to continual attack, both by reactive
species inside cells and by environmental agents. Toxic and mutagenic
consequences are minimized by distinct pathways of repair, and 130 known human DNA repair genes are described here. Notable features
presently include four enzymes that can remove uracil from DNA, seven
recombination genes related to RAD51, and many recently discovered DNA
polymerases that bypass damage, but only one system to remove the main
DNA lesions induced by ultraviolet light. More human DNA repair genes
will be found by comparison with model organisms and as common folds in
three-dimensional protein structures are determined. Modulation of DNA
repair should lead to clinical applications including improvement of
radiotherapy and treatment with anticancer drugs and an advanced
understanding of the cellular aging process.
1 Imperial Cancer Research Fund, Clare Hall
Laboratories, Blanche Lane, South Mimms, Herts EN6 3LD, UK.
2 Imperial Cancer Research Fund, 44 Lincoln's Inn
Fields, London WC2A 3PX, UK.
*
Present address: University of Pittsburgh Cancer Institute, S867
Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
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- Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer.
- O. Popanda, T. Schattenberg, C. T. Phong, D. Butkiewicz, A. Risch, L. Edler, K. Kayser, H. Dienemann, V. Schulz, P. Drings, et al. (2004)
Carcinogenesis
25, 2433-2441
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- UV Light-induced DNA Damage and Tolerance for the Survival of Nucleotide Excision Repair-deficient Human Cells.
- S. Nakajima, L. Lan, S.-i. Kanno, M. Takao, K. Yamamoto, A. P. M. Eker, and A. Yasui (2004)
J. Biol. Chem.
279, 46674-46677
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- Irofulven Cytotoxicity Depends on Transcription-Coupled Nucleotide Excision Repair and Is Correlated with XPG Expression in Solid Tumor Cells.
- F. Koeppel, V. Poindessous, V. Lazar, E. Raymond, A. Sarasin, and A. K. Larsen (2004)
Clin. Cancer Res.
10, 5604-5613
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- Gene Expression Analysis of Tumor Spheroids Reveals a Role for Suppressed DNA Mismatch Repair in Multicellular Resistance to Alkylating Agents.
- G. Francia, S. Man, B. Teicher, L. Grasso, and R. S. Kerbel (2004)
Mol. Cell. Biol.
24, 6837-6849
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- Human Nucleotide Excision Repair Efficiently Removes Chromium-DNA Phosphate Adducts and Protects Cells against Chromate Toxicity.
- M. Reynolds, E. Peterson, G. Quievryn, and A. Zhitkovich (2004)
J. Biol. Chem.
279, 30419-30424
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- Identification of Genetic Variants in Base Excision Repair Pathway and Their Associations with Risk of Esophageal Squamous Cell Carcinoma.
- B. Hao, H. Wang, K. Zhou, Y. Li, X. Chen, G. Zhou, Y. Zhu, X. Miao, W. Tan, Q. Wei, et al. (2004)
Cancer Res.
64, 4378-4384
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- Involvement of base excision repair in response to therapy targeted at thymidylate synthase.
- L. Li, S. H. Berger, and M. D. Wyatt (2004)
Mol. Cancer Ther.
3, 747-753
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- High Specificity of Quantitative Excision Repair Cross-Complementing 1 Messenger RNA Expression for Prediction of Minor Histopathological Response to Neoadjuvant Radiochemotherapy in Esophageal Cancer.
- U. Warnecke-Eberz, R. Metzger, F. Miyazono, S. E. Baldus, S. Neiss, J. Brabender, H. Schaefer, W. Doerfler, E. Bollschweiler, H. P. Dienes, et al. (2004)
Clin. Cancer Res.
10, 3794-3799
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- DNA repair in higher plants; photoreactivation is the major DNA repair pathway in non-proliferating cells while excision repair (nucleotide excision repair and base excision repair) is active in proliferating cells.
- S. Kimura, Y. Tahira, T. Ishibashi, Y. Mori, T. Mori, J. Hashimoto, and K. Sakaguchi (2004)
Nucleic Acids Res.
32, 2760-2767
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- A Large-Scale Screen for Mutagen-Sensitive Loci in Drosophila.
- A. Laurencon, C. M. Orme, H. K. Peters, C. L. Boulton, E. K. Vladar, S. A. Langley, E. P. Bakis, D. T. Harris, N. J. Harris, S. M. Wayson, et al. (2004)
Genetics
167, 217-231
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- Polymorphisms in DNA repair and metabolic genes in bladder cancer.
- S. Sanyal, F. Festa, S. Sakano, Z. Zhang, G. Steineck, U. Norming, H. Wijkstrom, P. Larsson, R. Kumar, and K. Hemminki (2004)
Carcinogenesis
25, 729-734
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- Interaction of human and bacterial AlkB proteins with DNA as probed through chemical cross-linking studies.
- Y. Mishina, C.-H. J. Lee, and C. He (2004)
Nucleic Acids Res.
32, 1548-1554
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- Expression of Base Excision DNA Repair Genes Is a Sensitive Biomarker for in Vivo Detection of Chemical-induced Chronic Oxidative Stress: Identification of the Molecular Source of Radicals Responsible for DNA Damage by Peroxisome Proliferators.
- I. Rusyn, S. Asakura, B. Pachkowski, B. U. Bradford, M. F. Denissenko, J. M. Peters, S. M. Holland, J. K. Reddy, M. L. Cunningham, and J. A. Swenberg (2004)
Cancer Res.
64, 1050-1057
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- Deficient Nucleotide Excision Repair Capacity Enhances Human Prostate Cancer Risk.
- J. J. Hu, M. C. Hall, L. Grossman, M. Hedayati, D. L. McCullough, K. Lohman, and L. D. Case (2004)
Cancer Res.
64, 1197-1201
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- DNA Repair Gene XRCC1 and XPD Polymorphisms and Risk of Prostate Cancer.
- B. A. Rybicki, D. V. Conti, A. Moreira, M. Cicek, G. Casey, and J. S. Witte (2004)
Cancer Epidemiol. Biomarkers Prev.
13, 23-29
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- Genetic Variation and Exposure Related Risk Estimation: Will Toxicology Enter a New Era? DNA Repair and Cancer as a Paradigm.
- H. W. Mohrenweiser (2004)
Toxicol Pathol
32, 136-145
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- MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation.
- Y. Wang and J. Qin (2003)
PNAS
100, 15387-15392
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- p53 Mutations in Bladder Cancer: Evidence for Exogenous versus Endogenous Risk Factors.
- J. C. Schroeder, K. Conway, Y. Li, K. Mistry, D. A. Bell, and J. A. Taylor (2003)
Cancer Res.
63, 7530-7538
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- Exposing the MYtH about base excision repair and human inherited disease.
- J. P. Cheadle and J. R. Sampson (2003)
Hum. Mol. Genet.
12, R159-R165
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- Base Excision Repair Intermediates Induce p53-independent Cytotoxic and Genotoxic Responses.
- R. W. Sobol, M. Kartalou, K. H. Almeida, D. F. Joyce, B. P. Engelward, J. K. Horton, R. Prasad, L. D. Samson, and S. H. Wilson (2003)
J. Biol. Chem.
278, 39951-39959
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- Relationship between XPG codon 1104 polymorphism and risk of primary lung cancer.
- H.-S. Jeon, K. M. Kim, S. H. Park, S. Y. Lee, J. E. Choi, G. Y. Lee, S. Kam, R. W. Park, I.-S. Kim, C. H. Kim, et al. (2003)
Carcinogenesis
24, 1677-1681
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