Mutations of GTBP in genetically unstable cells

Nickolas Papadopoulos; Nicholas C. Nicolaides; Bo Liu; Ramon Parsons; Christoph Lengauer; Fabio Palombo; Antonello D'Arrigo; Sanford Markowitz; James K.V. Willson; Kenneth W. Kinzler; Josef Jiricny; Bert Vogelstein

doi:10.1126/science.7604266

Mutations of GTBP in genetically unstable cells

Nickolas Papadopoulos, Nicholas C. Nicolaides, Bo Liu, Ramon Parsons, Christoph Lengauer, Fabio Palombo, Antonello D'Arrigo, Sanford Markowitz, James K.V. Willson, Kenneth W. Kinzler, Josef Jiricny, Bert Vogelstein

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457 Scopus citations

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 alter-ations 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.

Original language	English (US)
Pages (from-to)	1915-1917
Number of pages	3
Journal	Science
Volume	268
Issue number	5219
DOIs	https://doi.org/10.1126/science.7604266
State	Published - 1995

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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 alter-ations 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.",

author = "Nickolas Papadopoulos and Nicolaides, {Nicholas C.} and Bo Liu and Ramon Parsons and Christoph Lengauer and Fabio Palombo and Antonello D'Arrigo and Sanford Markowitz and Willson, {James K.V.} and Kinzler, {Kenneth W.} and Josef Jiricny and Bert Vogelstein",

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doi = "10.1126/science.7604266",

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T1 - Mutations of GTBP in genetically unstable cells

AU - Papadopoulos, Nickolas

AU - Nicolaides, Nicholas C.

AU - Liu, Bo

AU - Parsons, Ramon

AU - Lengauer, Christoph

AU - Palombo, Fabio

AU - D'Arrigo, Antonello

AU - Markowitz, Sanford

AU - Willson, James K.V.

AU - Kinzler, Kenneth W.

AU - Jiricny, Josef

AU - Vogelstein, Bert

PY - 1995

Y1 - 1995

N2 - 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 alter-ations 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.

AB - 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 alter-ations 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.

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Mutations of GTBP in genetically unstable cells

Abstract

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