Strand-specific mismatch correction in human cells occurs by a mechanism similar to that of the E. coli reaction, and like the bacterial pathway, the human system functions in mutation avoidance. Using an in vitro assay, we have identified mismatch repair defects in a number of hypermutable human cell lines, including a set of lines derived from RER+ tumors. More than 90% of the genetically unstable tumor cell lines tested to date are deficient in the reaction, suggesting that mismatch repair defects are associated with the vast majority of RER+ tumors. These hypermutable cell lines define several in vitro complementation groups, and activities that complement two of these have been isolated in pure form. hMutLα is a 1:1 complex of the MutL homologs MLH1 and PMS2, while tiMutSα is also a heterodimer of the MutS homologs MSH2 and p160 (GTBP). The hMutSα heterodimer specifically recognizes base-base mismatches, small insertion/deletion mispairs, and several types of chemical lesions.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology