Mice deficient in Msh2 and Mlh1 develop more tumors more quickly and have the shortest median survival times than mice deficient in other aspects of MMR [24, 46, 88, 92]. MSH2 and MLH1 are central to MMR function and are mutated with the highest frequencies in Lynch syndrome tumors, indicative of their pivotal importance in this DNA repair pathway, and the inherent selection required for their inactivation leading to tumorigenesis. Here, MLH1 is linked to Lynch syndrome.