Structure of a DNA glycosylase searching for lesions.
Publication Type:Journal Article
Source:Science, Volume 311, Issue 5764, p.1153-7 (2006)
Keywords:Base Pairing, Binding Sites, Cross-Linking Reagents, Crystallography, X-Ray, DNA, DNA Damage, DNA Glycosylases, Geobacillus stearothermophilus, Guanine, Hydrogen Bonding, Models, Molecular, Nucleic Acid Conformation, Oligodeoxyribonucleotides, Protein Conformation, Protein Structure, Secondary
<p>DNA glycosylases must interrogate millions of base pairs of undamaged DNA in order to locate and then excise one damaged nucleobase. The nature of this search process remains poorly understood. Here we report the use of disulfide cross-linking (DXL) technology to obtain structures of a bacterial DNA glycosylase, MutM, interrogating undamaged DNA. These structures, solved to 2.0 angstrom resolution, reveal the nature of the search process: The protein inserts a probe residue into the helical stack and severely buckles the target base pair, which remains intrahelical. MutM therefore actively interrogates the intact DNA helix while searching for damage.</p>