Insights into the glycosylase search for damage from single-molecule fluorescence microscopy

Andrea J Lee; David M Warshaw; Susan S Wallace

doi:10.1016/j.dnarep.2014.01.007

Insights into the glycosylase search for damage from single-molecule fluorescence microscopy

DNA Repair (Amst). 2014 Aug:20:23-31. doi: 10.1016/j.dnarep.2014.01.007. Epub 2014 Feb 20.

Authors

Andrea J Lee¹, David M Warshaw², Susan S Wallace³

Affiliations

¹ 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.
² 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.
³ 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.

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.

Keywords: Base excision repair; DNA glycosylases; DNA scanning; Facilitated diffusion; Single-molecule fluorescence microscopy.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Amino Acid Sequence
Animals
Base Sequence
DNA / chemistry*
DNA / metabolism
DNA Glycosylases / chemistry*
DNA Glycosylases / metabolism
DNA Repair*
Escherichia coli / enzymology
Escherichia coli / genetics
Humans
Microscopy, Fluorescence
Molecular Sequence Data
Protein Binding

Substances

DNA
DNA Glycosylases

Abstract

Publication types

MeSH terms

Substances

Grants and funding