title: DNA glycosylases search for and remove oxidized DNA bases.
abstract: This review article presents, an overview of the DNA glycosylases that recognize oxidized DNA bases using the Fpg/Nei family of DNA glycosylases as models for how structure can inform function. For example, even though human NEIL1 and the plant and fungal orthologs lack the zinc finger shown to be required for binding, DNA crystal structures revealed a "zincless finger" with the same properties. Moreover, the "lesion recognition loop" is not involved in lesion recognition, rather, it stabilizes 8-oxoG in the active site pocket. Unlike the other Fpg/Nei family members, Neil3 lacks two of the three void-filling residues that stabilize the DNA duplex and interact with the opposite strand to the damage which may account for its preference for lesions in single-stranded DNA. Also single-molecule approaches show that DNA glycosylases search for their substrates in a sea of undamaged DNA by using a wedge residue that is inserted into the DNA helix to probe for the presence of damage.
authors.affiliation: Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, Vermont.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Wallace
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D045647:DNA Glycosylases / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction
chemical_list: D004247:DNA; D045647:DNA Glycosylases
keywords: DNA base damage; DNA glycosylase; Fpg/Nei family of DNA glycosylases; Neil3; eukaryotic Neil glycosylases; glycosylase crystal structures; glycosylase search; glycosylase substrate specificity; oxidative DNA damage; single-molecule studies