Defective mismatch-repair function is associated with hereditary nonpolyposis colorectal cancer (HNPCC), and mutations in the MLH1 subunit of the MutLα heterodimer MLH1–PMS1 underlie half of HNPCC cases. Structural analysis of the conserved C-terminal domain of Mlh1 from budding yeast shows that Mlh1 contributes to the functionally important Pms1 endonuclease site and provides a rationale for the deleterious impact of MLH1 mutations.
- Emeric Gueneau
- Claudine Dherin
- Jean-Baptiste Charbonnier
