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Substrate spectrum of human excinuclease: repair of abasic sites, methylated bases, mismatches, and bulky adducts.
Open accessAbstract
Nucleotide-excision repair is the repair system for removing bulky lesions from DNA. Humans deficient in this repair pathway suffer from xeroderma pigmentosum (XP), a disease characterized by photodermatoses, including skin cancers. At the cellular level, XP patients fail to remove cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts induced by UV light, as well as other bulky DNA lesions caused by various genotoxic agents. XP cells are not particularly sensitive to ionizing radiation or to alkylating agents that cause mostly nonbulky DNA lesions. Therefore, it has generally been assumed that the human nucleotide-excision repair enzyme (excinuclease) is specific for bulky adducts. To determine the substrate range of human excinuclease we used the highly sensitive excision assay and tested bulky adducts, synthetic apurinic/apyrimidinic sites, N6-methyladenine, O6-methylguanine, and mismatches as potential substrates. We found that all of these "lesions" were removed by human excinuclease, although with vastly different efficiencies.
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Citations
Cited by
Mechanisms of DNA damage, repair, and mutagenesis
Chatterjee, N., & Walker, G. C. (2017) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22087 · Cited by 2,039
“…by an a-ketoglutarate-dependent dioxygenase AlkB homolog and (2) BER, which is initiated by DNA glycosylases to remove the methylated bases by catalyzing the cleavage of their glycosidic bonds [Sakumi and Sekiguchi, 1990; Tudek et al., 1992; Huang et al., 1994; Zak et al., 1994; Ye et al., 1998].”
Mechanisms of DNA Excision Repair
Sancar, A. (1994) · Science · doi:10.1126/science.7801120 · Cited by 555
Self-citationReconstitution of Human DNA Repair Excision Nuclease in a Highly Defined System
Mu, D., Park, C.-H., Matsunaga, T., Hsu, D. S., Reardon, J. T., & Sancar, A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.6.2415 · Cited by 476
Self-citationReardon, J. T., Bessho, T., Kung, H. C., Bolton, P. H., & Sancar, A. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.17.9463 · Cited by 366
Self-citationReardon, J. T., & Sancar, A. (2005) · Progress in Nucleic Acid Research and Molecular Biology · doi:10.1016/s0079-6603(04)79004-2 · Cited by 350
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Metadata
- Authors
- Huang, J. C., Hsu, D. S., Kazantsev, A., & Sancar, A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1994-12-06
- Volume
- 91
- Issue
- 25
- Pages
- 12213-12217
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2000856801
- Cited by
- 230
- References
- 0
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- green
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- Huang, J. C., Hsu, D. S., Kazantsev, A., & Sancar, A. (1994). Substrate spectrum of human excinuclease: repair of abasic sites, methylated bases, mismatches, and bulky adducts. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.91.25.12213
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