The mouse ortholog of NEIL3 is a functional DNA glycosylase in vitro and in vivo
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- Minmin Liu
- Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405-0086;
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- Viswanath Bandaru
- Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405-0086;
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- Jeffrey P. Bond
- Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405-0086;
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- Pawel Jaruga
- Chemical Science and Technology Laboratory, National Institute of Standards and Technology, Building 227/A243, Gaithersburg, MD 20899;
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- Xiaobei Zhao
- Department of Chemistry, University of Utah, Salt Lake City, UT 84112-0850; and
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- Plamen P. Christov
- Departments of Chemistry and Biochemistry and Center in Molecular Toxicology, Vanderbilt University, Nashville, TN 37235-1822
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- Cynthia J. Burrows
- Department of Chemistry, University of Utah, Salt Lake City, UT 84112-0850; and
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- Carmelo J. Rizzo
- Departments of Chemistry and Biochemistry and Center in Molecular Toxicology, Vanderbilt University, Nashville, TN 37235-1822
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- Miral Dizdaroglu
- Chemical Science and Technology Laboratory, National Institute of Standards and Technology, Building 227/A243, Gaithersburg, MD 20899;
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- Susan S. Wallace
- Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405-0086;
書誌事項
- 公開日
- 2010-02-25
- DOI
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- 10.1073/pnas.0908307107
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:p> To protect cells from oxidative DNA damage and mutagenesis, organisms possess multiple glycosylases to recognize the damaged bases and to initiate the Base Excision Repair pathway. Three DNA glycosylases have been identified in mammals that are homologous to the <jats:italic>Escherichia coli</jats:italic> Fpg and Nei proteins, Neil1, Neil2, and Neil3. Neil1 and Neil2 in human and mouse have been well characterized while the properties of the Neil3 protein remain to be elucidated. In this study, we report the characterization of <jats:italic>Mus musculus</jats:italic> (house mouse) Neil3 (MmuNeil3) as an active DNA glycosylase both in vitro and in vivo. In duplex DNA, MmuNeil3 recognizes the oxidized purines, spiroiminodihydantoin (Sp), guanidinohydantoin (Gh), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) and 4,6-diamino- 5-formamidopyrimidine (FapyA), but not 8-oxo-7,8-dihydroguanine (8-oxoG). Interestingly, MmuNeil3 prefers lesions in single-stranded DNA and in bubble structures. In contrast to other members of the family that use the N-terminal proline as the nucleophile, MmuNeil3 forms a Schiff base intermediate via its N-terminal valine. We expressed the glycosylase domain of MmuNeil3 (MmuNeil3Δ324) in an <jats:italic>Escherichia coli</jats:italic> triple mutant lacking Fpg, Nei, and MutY glycosylase activities and showed that MmuNeil3 greatly reduced both the spontaneous mutation frequency and the level of FapyG in the DNA, suggesting that Neil3 plays a role in repairing FapyG in vivo. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 107 (11), 4925-4930, 2010-02-25
Proceedings of the National Academy of Sciences
