Fig. 7.

Model for early stages of MMR. (A) Model summarizing how MutSα finds lesions, how MutLα locates lesion-bound MutSα, and how the MutSα/MutLα scans the flanking DNA by 1D diffusion after ATP-triggered release from a lesion. (B) MutSα structural changes predicted upon ATP-triggered release from a lesion. (Left) The structures represent front and side views of mismatch-bound human MutSα (Protein Data Bank ID code 2O8B) in which the protein complex (gray) is wrapped around the DNA (green) with domain I of Msh6 (magenta) engaged with the mismatched base (33). (Right) Hypothetical structures were obtained by rigid-body rotation of Msh6 domain I out of the major groove to illustrate how retraction of Msh6 domain I out of the DNA major groove might allow the release of MutSα from the mismatch and still allow the protein to remain tightly wrapped around the DNA while enabling 1D diffusion in the absence of an obligatory rotational component.