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Significance Base excision repair, an evolutionarily conserved process responsible for the repair of most endogenous damage, is initiated by DNA glycosylases. Observation of the motion of single molecules of three bacterial glycosylases in two structural families, Fpg, Nei, and Nth, together with mutational analysis, has demonstrated that both families use a wedge residue to scan DNA for damage. Glycosylases pause during diffusion to interrogate bases and upon encountering a damage stop to evert and excise it. Moreover, we have derived a simple chemomechanical simulation that fits our data and is in agreement with ensemble studies.

Two glycosylase families diffusively scan DNA using a wedge residue to probe for and identify oxidatively damaged bases