title: Mutations of GTBP in genetically unstable cells.
abstract: The molecular defects responsible for tumor cell hypermutability in humans 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 mismatch repair genes, which display widespread alterations in mononucleotide, dinucleotide, and other simple repeated sequences, the GTBP-deficient cells showed alterations primarily in mononucleotide tracts. These results suggest that GTBP is important for maintaining the integrity of the human genome and document molecular defects accounting for variation in mutator phenotype.
authors.affiliation: Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.
authors.forename: N
authors.initials: N
authors.lastname: Papadopoulos
authors.forename: N C
authors.initials: NC
authors.lastname: Nicolaides
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.forename: R
authors.initials: R
authors.lastname: Parsons
authors.forename: C
authors.initials: C
authors.lastname: Lengauer
authors.forename: F
authors.initials: F
authors.lastname: Palombo
authors.forename: A
authors.initials: A
authors.lastname: D'Arrigo
authors.forename: S
authors.initials: S
authors.lastname: Markowitz
authors.forename: J K
authors.initials: JK
authors.lastname: Willson
authors.forename: K W
authors.initials: KW
authors.lastname: Kinzler
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003062:Codon; D015179:Colorectal Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D004276:DNA, Satellite / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D016368:Frameshift Mutation; D005819:Genetic Markers; D018095:Germ-Line Mutation; D006801:Humans; D008969:Molecular Sequence Data; D014407:Tumor Cells, Cultured
chemical_list: D003062:Codon; D004273:DNA, Neoplasm; D004276:DNA, Satellite; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D005819:Genetic Markers