Figure 2.

Hypothesized conformational capture and correlated motion mechanisms for lesion recognition by Rad4. (A) Conformational capture mechanism. The ensemble of damaged duplexes contains a population that has one or two bases opposite the lesion flipped out. The Rad4 scans the damaged DNA, flipped out bases in a locally destabilized region are captured by the BHD2 and BHD3 domains, and the BHD3 β-hairpin inserts with eviction of the lesion. (B) Correlated motion mechanism. Scanning is accompanied by probing for a locally destabilized region by BHD2 and BHD3 domains. Once a sufficiently destabilized region is sensed, in correlated motion the BHD3 β-hairpin inserts, the lesion is evicted, and the partner bases flip out to associate with BHD2 and BHD3 domains; the order of these events may be lesion-dependent.