Mechanism of translocation of uracil-DNA glycosylase from Escherichia coli between distributed lesions

► Uracil-DNA glycosylase (Ung) excises uracil bases from DNA. ► Ung searches for these lesions by combining diffusion in 3D and random sliding in 1D. ► Mg2+ ions suppress the 1D search by Ung in double-stranded DNA. ► Ung can efficiently search through short single-stranded gaps within double-stranded DNA. ► The characteristic Ung 1D search distance is ∼100 nucleotides, and the translocation rate constant is ∼2 × 106 s−1.