MUTATIONS OF GTBP IN GENETICALLY UNSTABLE CELLS

The molecular defects responsible for tumor cell hypermutability in hu mans have not yet been fully identified. Here the gene encoding a G/T mismatch-binding protein (GTBP) was localized to within 1 megabase of the related hMSH2 gene on chromosome 2 and was found to be inactivated in three hypermutable cell lines. Unlike cells defective in other mis match repair genes, which display widespread alterations in mononucleo tide, dinucleotide, and other simple repeated sequences, the GTBP-defi cient cells showed alterations primarily in mononucleotide tracts. The se results suggest that GTBP is important for maintaining the integrit y of the human genome and document molecular defects accounting for va riation in mutator phenotype.