SINGLE-GENE COMPLEMENTATION OF THE HPMS2 DEFECT IN HEC-1-A ENDOMETRIAL CARCINOMA-CELLS

Results from the analysis of human tumor cell lines with mutations in DNA mismatch repair genes have contributed to the understanding of the functions of these gene products in DNA mismatch repair, microsatelli te instability, cell cycle checkpoint control, transcription-coupled n ucleotide excision repair, and resistance to cytotoxic agents. However , complementation of human DNA mismatch repair defects by introduction of a single cloned gene or cDNA,,which would serve to directly prove or disprove their involvement in these processes, has not been accompl ished. sere, we introduce a wild-type copy of the hPMS2 cDNA by stable transfection into the PMS2 mutant HEC-1-A cell Line. HEC-1-A cells ex pressing wild type hPMS2 exhibit increased microsatellite stability, h ave a reduced mutation rate at the endogenous hypoxanthine phosphoribo syltransferase locus and extracts from these cells are able to perform strand-specific mismatch repair, These results demonstrate that the h PMS2 gene is integral to the maintenance of genome stability.