title: Direct visualization of a DNA glycosylase searching for damage.
abstract: DNA glycosylases preserve the integrity of genetic information by recognizing damaged bases in the genome and catalyzing their excision. It is unknown how DNA glycosylases locate covalently modified bases hidden in the DNA helix amongst vast numbers of normal bases. Here we employ atomic-force microscopy (AFM) with carbon nanotube probes to image search intermediates of human 8-oxoguanine DNA glycosylase (hOGG1) scanning DNA. We show that hOGG1 interrogates DNA at undamaged sites by inducing drastic kinks. The sharp DNA bending angle of these non-lesion-specific search intermediates closely matches that observed in the specific complex of 8-oxoguanine-containing DNA bound to hOGG1. These findings indicate that hOGG1 actively distorts DNA while searching for damaged bases.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Liwei
authors.initials: L
authors.lastname: Chen
authors.forename: Karl A
authors.initials: KA
authors.lastname: Haushalter
authors.forename: Charles M
authors.initials: CM
authors.lastname: Lieber
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Verdine
mesh_terms: D020029:Base Pairing; D004249:DNA Damage / Q000235:genetics*; D043382:DNA-Formamidopyrimidine Glycosylase; D006801:Humans; D018625:Microscopy, Atomic Force; D009699:N-Glycosyl Hydrolases / Q000032:analysis* / Q000235:genetics
chemical_list: D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase