title: Insights into the glycosylase search for damage from single-molecule fluorescence microscopy.
abstract: The first step of base excision repair utilizes glycosylase enzymes to find damage within a genome. A persistent question in the field of DNA repair is how glycosylases interact with DNA to specifically find and excise target damaged bases with high efficiency and specificity. Ensemble studies have indicated that glycosylase enzymes rely upon both sliding and distributive modes of search, but ensemble methods are limited in their ability to directly observe these modes. Here we review insights into glycosylase scanning behavior gathered through single-molecule fluorescence studies of enzyme interactions with DNA and provide a context for these results in relation to ensemble experiments.
authors.affiliation: Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, The University of Vermont, 95 Carrigan Drive, Stafford Hall, Burlington, VT 05405-0084, USA. Electronic address: Andrea.Lee@uvm.edu.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Lee
authors.affiliation: Department of Molecular Physiology and Biophysics, The University of Vermont, Health Science Research Facility, 149 Beaumont Avenue, Burlington, VT 05405-0075, USA. Electronic address: David.Warshaw@uvm.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Warshaw
authors.affiliation: Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, The University of Vermont, 95 Carrigan Drive, Stafford Hall, Burlington, VT 05405-0084, USA. Electronic address: Susan.Wallace@uvm.edu.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Wallace
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D045647:DNA Glycosylases / Q000737:chemistry* / Q000378:metabolism; D004260:DNA Repair; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D011485:Protein Binding
chemical_list: D004247:DNA; D045647:DNA Glycosylases
keywords: Base excision repair; DNA glycosylases; DNA scanning; Facilitated diffusion; Single-molecule fluorescence microscopy