Neil3, the final frontier for the DNA glycosylases that recognize oxidative damage

doi:10.1016/j.mrfmmm.2012.12.003

Review

. 2013 Mar-Apr:743-744:4-11.

doi: 10.1016/j.mrfmmm.2012.12.003. Epub 2012 Dec 26.

Neil3, the final frontier for the DNA glycosylases that recognize oxidative damage

Minmin Liu¹, Sylvie Doublié², Susan S Wallace³

Affiliations

¹ Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Dr., Burlington, VT 05405-0086, United States. Electronic address: minminli@usc.edu.
² Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Dr., Burlington, VT 05405-0086, United States.
³ Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Dr., Burlington, VT 05405-0086, United States. Electronic address: susan.wallace@uvm.edu.

PMID: 23274422
PMCID: PMC3657305
DOI: 10.1016/j.mrfmmm.2012.12.003

Review

Neil3, the final frontier for the DNA glycosylases that recognize oxidative damage

Minmin Liu et al. Mutat Res. 2013 Mar-Apr.

. 2013 Mar-Apr:743-744:4-11.

doi: 10.1016/j.mrfmmm.2012.12.003. Epub 2012 Dec 26.

Authors

Minmin Liu¹, Sylvie Doublié², Susan S Wallace³

Affiliations

¹ Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Dr., Burlington, VT 05405-0086, United States. Electronic address: minminli@usc.edu.
² Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Dr., Burlington, VT 05405-0086, United States.
³ Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Dr., Burlington, VT 05405-0086, United States. Electronic address: susan.wallace@uvm.edu.

PMID: 23274422
PMCID: PMC3657305
DOI: 10.1016/j.mrfmmm.2012.12.003

Abstract

DNA glycosylases are the enzymes that initiate the Base Excision Repair (BER) process that protects all organisms from the mutagenic and/or cytotoxic effects of DNA base lesions. Endonuclease VIII like proteins (Neil1, Neil2 and Neil3) are found in vertebrate genomes and are homologous to the well-characterized bacterial DNA glycosylases, Formamidopyrimidine DNA glycosylase (Fpg) and Endonuclease VIII (Nei). Since the initial discovery of the Neil proteins, much progress has been made on characterizing Neil1 and Neil2. It was not until recently, however, that Neil3 was shown to be a functional DNA glycosylase having a different substrate specificity and unusual structural features compared with other Fpg/Nei homologs. Although the biological functions of Neil3 still remain an enigma, this review highlights recent biochemical and structural data that may ultimately shed light on its biological role.

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Figures

**Figure 1**
Alignment of the structural features of NEIL3 with representative members of the Fpg/Nei family. Domains and motifs in the scheme are described in the box below. Sequences of the conserved N-terminus are shown in the bracket. NEIL1: human NEIL1; NEIL2: human NEIL2; EcoNei: *Escherichia coli* Nei; EcoFpg: *Escherichia coli* Fpg.

**Figure 2**
Structural comparison of MmuNeil3 (colored in green) with NEIL1 (colored in red). (A) Superposition of the glycosylase domain of MmuNeil3 with that of NEIL1 (PDB ID code 1TDZ [99]). The N-terminal proline of NEIL1 and N-terminal valine of MmuNeil3 are represented as a stick model, and the zinc metal ion in MmuNeil3 is shown as a green sphere. (B) Close-up view of the ! F-! 9 loop. Superposition of the ! F-! 9 loop from MmuNeil3! 324 (residues 224-248) with that of NEIL1 (residues 228-261). The flipped-out 8-oxoG from the *Bacillus stearothermophilus* Fpg-DNA complex (PDB ID code: 1R2Y; [100]) is shown in orange. (C) Close-up view of the “void-filling residues” (Met81, Arg118 and Phe120 for NEIL1, and Met99 for MmuNeil3! 324).

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References

1. Mitra S, Izumi T, Boldogh I, Bhakat KK, Hill JW, Hazra TK. Choreography of oxidative damage repair in mammalian genomes. Free radical biology & medicine. 2002;33:15–28. - PubMed
1. Barnes DE, Lindahl T. Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annual review of genetics. 2004;38:445–476. - PubMed
1. Zharkov DO. Base excision DNA repair. Cellular and molecular life sciences: CMLS. 2008;65:1544–1565. - PMC - PubMed
1. Duclos S, Doublie S, Wallace SS. Consequences and Repair of Oxidative DNA Damage. In: Greim H, Albertini RJ, editors. Issues in Toxicology: The Cellular Response to the Genotoxic Insult: The Question of Threshold for Genotoxic Carcinogens. The Royal Society of Chemistry; London: 2012. pp. 109–152.
1. Blainey PC, van Oije AM, Banerjee A, Verdine GL, Xie XS. A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA. Proc Natl Acad Sci U S A. 2006;103:5752–5757. - PMC - PubMed

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[1] Mitra S, Izumi T, Boldogh I, Bhakat KK, Hill JW, Hazra TK. Choreography of oxidative damage repair in mammalian genomes. Free radical biology & medicine. 2002;33:15–28. - PubMed

[2] Mitra S, Izumi T, Boldogh I, Bhakat KK, Hill JW, Hazra TK. Choreography of oxidative damage repair in mammalian genomes. Free radical biology & medicine. 2002;33:15–28. - PubMed

[3] Barnes DE, Lindahl T. Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annual review of genetics. 2004;38:445–476. - PubMed

[4] Barnes DE, Lindahl T. Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annual review of genetics. 2004;38:445–476. - PubMed

[5] Zharkov DO. Base excision DNA repair. Cellular and molecular life sciences: CMLS. 2008;65:1544–1565. - PMC - PubMed

[6] Zharkov DO. Base excision DNA repair. Cellular and molecular life sciences: CMLS. 2008;65:1544–1565. - PMC - PubMed

[7] Duclos S, Doublie S, Wallace SS. Consequences and Repair of Oxidative DNA Damage. In: Greim H, Albertini RJ, editors. Issues in Toxicology: The Cellular Response to the Genotoxic Insult: The Question of Threshold for Genotoxic Carcinogens. The Royal Society of Chemistry; London: 2012. pp. 109–152.

[8] Duclos S, Doublie S, Wallace SS. Consequences and Repair of Oxidative DNA Damage. In: Greim H, Albertini RJ, editors. Issues in Toxicology: The Cellular Response to the Genotoxic Insult: The Question of Threshold for Genotoxic Carcinogens. The Royal Society of Chemistry; London: 2012. pp. 109–152.

[9] Blainey PC, van Oije AM, Banerjee A, Verdine GL, Xie XS. A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA. Proc Natl Acad Sci U S A. 2006;103:5752–5757. - PMC - PubMed

[10] Blainey PC, van Oije AM, Banerjee A, Verdine GL, Xie XS. A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA. Proc Natl Acad Sci U S A. 2006;103:5752–5757. - PMC - PubMed

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Neil3, the final frontier for the DNA glycosylases that recognize oxidative damage

Affiliations

Neil3, the final frontier for the DNA glycosylases that recognize oxidative damage

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