ISOLATION OF AN HMSH2-P160 HETERODIMER THAT RESTORES DNA MISMATCH REPAIR TO TUMOR-CELLS

A mismatch-binding heterodimer of hMSH2 and a 160-kilodalton polypepti de has been isolated from Hela cells by virtue of its ability to resto re mismatch repair to nuclear extracts of hMSH2-deficient LoVo colorec tal tumor cells. This heterodimer, designated hMutS alpha; also restor es mismatch repair to extracts of alkylation-tolerant MT1 lymphoblasto id cells and HCT-15 colorectal tumor cells, which are selectively defe ctive in the repair of base-base and single-nucleotide insertion-delet ion mismatches. Because HCT-15 cells appear to be free of hMSH2 mutati ons, this selective repair defect is likely a result of a deficiency o f the hMutS alpha 160-kilodalton subunit, and mutations in the corresp onding gene may confer hypermutability and cancer predisposition.