We have now discovered that eukaryotes, including mammals, have a DNA mismatch repair pathway analogous to the pathway that exists in bacteria. Defects or alterations in this mismatch repair pathway in a mammal, such as a human, will result in the accumulation of unstable repeated DNA sequences. Such a phenotype has a high correlation to disease state in a number of cancers, such as hereditary colon cancers. Accordingly, discovering a defect or alteration in the pathway can be diagnostic of a predisposition to cancer, and prognostic for a particular cancer. We have also discovered and sequenced one of the genes in this pathway in a number of mammals, including humans. This gene, referred to herein as MSH2, has many applications. It can be used in assays, to express gene product, for drug screens, and therapeutically. We also disclose herein a method for screening for other genes in this mismatch repair pathway.