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Science 30 June 1995:
Vol. 268. no. 5219, pp. 1915 - 1917
DOI: 10.1126/science.7604266
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Articles

Science, Vol 268, Issue 5219, 1915-1917
Copyright © 1995 by American Association for the Advancement of Science

articles

Mutations of GTBP in genetically unstable cells

N Papadopoulos, NC Nicolaides, B Liu, R Parsons, C Lengauer, F Palombo, A D'Arrigo, S Markowitz, JK Willson, KW Kinzler, and al. et

Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.

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.


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Specificity of Mutations Induced by the Food-associated Heterocyclic Amine 2-Amino-1-methyl-6-phenylimidazo-[4,5-b]-pyridine in Colon Cancer Cell Lines Defective in Mismatch Repair.
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DNA mismatch repair genes and colorectal cancer.
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Gut 47, 148-153
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Incidence of germline hMLH1 and hMSH2 mutations (HNPCC patients) among newly diagnosed colorectal cancers in a Slovenian population.
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Nucleic Acids Res. 28, e44
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Standardized Approach for Microsatellite Instability Detection in Colorectal Carcinomas.
I. Gonzalez-Garcia, V. Moreno, M. Navarro, J. Marti-Rague, E. Marcuello, C. Benasco, O. Campos, G. Capella, and M. A. Peinado (2000)
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hMSH6 Alterations in Patients with Microsatellite Instability-Low Colorectal Cancer.
Y. R. Parc, K. C. Halling, L. Wang, E. R. Christensen, J. M. Cunningham, A. J. French, L. J. Burgart, T. L. Price-Troska, P. C. Roche, and S. N. Thibodeau (2000)
Cancer Res. 60, 2225-2231
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Detection of Microsatellite Instability by Fluorescence Multiplex Polymerase Chain Reaction.
K. D. Berg, C. L. Glaser, R. E. Thompson, S. R. Hamilton, C. A. Griffin, and J. R. Eshleman (2000)
J. Mol. Diagn. 2, 20-28
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Mutation in the Magnesium Binding Site of hMSH6 Disables the hMutSalpha Sliding Clamp from Translocating along DNA.
I. Iaccarino, G. Marra, P. Dufner, and J. Jiricny (2000)
J. Biol. Chem. 275, 2080-2086
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Genetic Analysis of Mouse Embryonic Stem Cells Bearing Msh3 and Msh2 Single and Compound Mutations.
A. Abuin, H. Zhang, and A. Bradley (2000)
Mol. Cell. Biol. 20, 149-157
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Heterozygous Germ Line hCHK2 Mutations in Li-Fraumeni Syndrome.
D. W. Bell, J. M. Varley, T. E. Szydlo, D. H. Kang, D. C. Wahrer, K. E. Shannon, M. Lubratovich, S. J. Verselis, K. J. Isselbacher, J. F. Fraumeni, et al. (1999)
Science 286, 2528-2531
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hMLH1 Promoter Hypermethylation Is an Early Event in Human Endometrial Tumorigenesis.
M. Esteller, L. Catasus, X. Matias-Guiu, G. L. Mutter, J. Prat, S. B. Baylin, and J. G. Herman (1999)
Am. J. Pathol. 155, 1767-1772
   Abstract »    Full Text »    PDF »
hMutSalpha - and hMutLalpha -dependent phosphorylation of p53 in response to DNA methylator damage.
D. R. Duckett, S. M. Bronstein, Y. Taya, and P. Modrich (1999)
PNAS 96, 12384-12388
   Abstract »    Full Text »    PDF »
Mutator Phenotype in Human Hematopoietic Neoplasms and Its Association With Deletions Disabling DNA Repair Genes and bcl-2 Rearrangements.
S. Indraccolo, S. Minuzzo, L. Nicoletti, E. Cretella, M. Simon, G. Papakonstantinou, R. Hehlmann, M. Mion, R. Bertorelle, J. Roganovic, et al. (1999)
Blood 94, 2424-2432
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Biochemical Characterization of the Interaction between the Saccharomyces cerevisiae MSH2-MSH6 Complex and Mispaired Bases in DNA.
G. T. Marsischky and R. D. Kolodner (1999)
J. Biol. Chem. 274, 26668-26682
   Abstract »    Full Text »    PDF »
Role of DNA mismatch repair and p53 in signaling induction of apoptosis by alkylating agents.
M. J. Hickman and L. D. Samson (1999)
PNAS 96, 10764-10769
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Mononucleotide microsatellite instability and germline MSH6 mutation analysis in early onset colorectal cancer.
L. Verma, M. F Kane, C. Brassett, J. Schmeits, D G. R Evans, R. D Kolodner, and E. R Maher (1999)
J. Med. Genet. 36, 678-682
   Abstract »    Full Text »
Mechanisms of inactivation of mismatch repair genes in human colorectal cancer cell lines: The predominant role of hMLH1.
J. M. D. Wheeler, N. E. Beck, H. C. Kim, I. P. M. Tomlinson, N. J. McC. Mortensen, and W. F. Bodmer (1999)
PNAS 96, 10296-10301
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Polymorphic Variation at the BAT-25 and BAT-26 Loci in Individuals of African Origin : Implications for Microsatellite Instability Testing.
R. Pyatt, R. B. Chadwick, C. K. Johnson, C. Adebamowo, A. de la Chapelle, and T. W. Prior (1999)
Am. J. Pathol. 155, 349-353
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Sequence-dependent mutations in a shuttle vector plasmid replicated in a mismatch repair deficient human cell line.
S. E. Tobi, D. D. Levy, M. M. Seidman1, and K. H. Kraemer1 (1999)
Carcinogenesis 20, 1293-1301
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Microsatellite Instability Is Uncommon in Breast Cancer.
R. Anbazhagan, H. Fujii, and E. Gabrielson (1999)
Clin. Cancer Res. 5, 839-844
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Repair of Large Insertion/Deletion Heterologies in Human Nuclear Extracts Is Directed by a 5' Single-strand Break and Is Independent of the Mismatch Repair System.
S. J. Littman, W.-h. Fang, and P. Modrich (1999)
J. Biol. Chem. 274, 7474-7481
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Effect of hMSH6 cDNA expression on the phenotype of mismatch repair-deficient colon cancer cell line HCT15.
T. Lettieri, G. Marra, G. Aquilina, M. Bignami, N. E.A. Crompton, F. Palombo, and J. Jiricny (1999)
Carcinogenesis 20, 373-382
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Mismatch repair and differential sensitivity of mouse and human cells to methylating agents.
O. Humbert, S. Fiumicino, G. Aquilina, P. Branch, S. Oda, A. Zijno, P. Karran, and M. Bignami (1999)
Carcinogenesis 20, 205-214
   Abstract »    Full Text »    PDF »
MSH3 deficiency is not sufficient for a mutator phenotype in Chinese hamster ovary cells.
J. M. Hinz and M. Meuth (1999)
Carcinogenesis 20, 215-220
   Abstract »    Full Text »    PDF »
Malignancies of the Uterine Corpus and Immunoreactivity Score of the DNA "Mismatch-Repair" Enzyme Human Mut-S-Homologon-2.
M. Friedrich, C. Villena–Heinsen, K. Reitnauer, W. Schmidt, W. Tilgen, and J. Reichrath (1999)
J. Histochem. Cytochem. 47, 113-118
   Abstract »    Full Text »
Characterization of Distinct Human Endometrial Carcinoma Cell Lines Deficient in Mismatch Repair That Originated from a Single Tumor.
W. E. Glaab, J. I. Risinger, A. Umar, T. A. Kunkel, J. C. Barrett, and K. R. Tindall (1998)
J. Biol. Chem. 273, 26662-26669
   Abstract »    Full Text »    PDF »
Accumulated Clonal Genetic Alterations in Familial and Sporadic Colorectal Carcinomas with Widespread Instability in Microsatellite Sequences.
T. Fujiwara, J. M. Stolker, T. Watanabe, A. Rashid, P. Longo, J. R. Eshleman, S. Booker, H. T. Lynch, J. R. Jass, J. S. Green, et al. (1998)
Am. J. Pathol. 153, 1063-1078
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Microsatellite Instability and Mutation of DNA Mismatch Repair Genes in Gliomas.
S. Y. Leung, T. L. Chan, L. P. Chung, A. S. Y. Chan, Y. W. Fan, K. N. Hung, W. K. Kwong, J. W. C. Ho, and S. T. Yuen (1998)
Am. J. Pathol. 153, 1181-1188
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Involvement of the Mismatch Repair System in Temozolomide-Induced Apoptosis.
S. D'Atri, L. Tentori, P. M. Lacal, G. Graziani, E. Pagani, E. Benincasa, G. Zambruno, E. Bonmassar, and J. Jiricny (1998)
Mol. Pharmacol. 54, 334-341
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Small Slipped Register Genetic Instabilities in Escherichia coli in Triplet Repeat Sequences Associated with Hereditary Neurological Diseases.
R. D. Wells, P. Parniewski, A. Pluciennik, A. Bacolla, R. Gellibolian, and A. Jaworski (1998)
J. Biol. Chem. 273, 19532-19541
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Isolation of MutSbeta from Human Cells and Comparison of the Mismatch Repair Specificities of MutSbeta and MutSalpha.
J. Genschel, S. J. Littman, J. T. Drummond, and P. Modrich (1998)
J. Biol. Chem. 273, 19895-19901
   Abstract »    Full Text »    PDF »
Mismatch repair deficiency associated with overexpression of the MSH3 gene.
G. Marra, I. Iaccarino, T. Lettieri, G. Roscilli, P. Delmastro, and J. Jiricny (1998)
PNAS 95, 8568-8573
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Prediction-based threading of the hMSH2 DNA mismatch repair protein.
M. De las Alas, R. A. M. de bruin, L. T. Eyck, G. Los, and S. B. Howell (1998)
FASEB J 12, 653-663
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The Mutation Rate and Cancer.
A. L. Jackson and L. A. Loeb (1998)
Genetics 148, 1483-1490
   Abstract »    Full Text »    PDF »
Functional Overlap in Mismatch Repair by Human MSH3 and MSH6.
A. Umar, J. I. Risinger, W. E. Glaab, K. R. Tindall, J. C. Barrett, and T. A. Kunkel (1998)
Genetics 148, 1637-1646
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The role of microsatellite instability in gastric carcinoma.
J D HAYDEN, I G MARTIN, L CAWKWELL, and P QUIRKE (1998)
Gut 42, 300-303
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Mismatch Repair Defects and O6-Methylguanine-DNA Methyltransferase Expression in Acquired Resistance to Methylating Agents in Human Cells.
R. Hampson, O. Humbert, P. Macpherson, G. Aquilina, and P. Karran (1997)
J. Biol. Chem. 272, 28596-28606
   Abstract »    Full Text »    PDF »
Alternative genetic pathways in colorectal carcinogenesis.
S. Olschwang, R. Hamelin, P. Laurent-Puig, B. Thuille, Y. De Rycke, Y.-J. Li, F. Muzeau, J. Girodet, R.-J. Salmon, and G. Thomas (1997)
PNAS 94, 12122-12127
   Abstract »    Full Text »    PDF »
DHFR/MSH3 amplification in methotrexate-resistant cells alters the hMutSalpha /hMutSbeta ratio and reduces the efficiency of base-base mismatch repair.
J. T. Drummond, J. Genschel, E. Wolf, and P. Modrich (1997)
PNAS 94, 10144-10149
   Abstract »    Full Text »    PDF »
DNA Polymerase delta Is Required for Human Mismatch Repair in Vitro.
M. J. Longley, A. J. Pierce, and P. Modrich (1997)
J. Biol. Chem. 272, 10917-10921
   Abstract »    Full Text »    PDF »
Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2.
L. Narayanan, J. A. Fritzell, S. M. Baker, R. M. Liskay, and P. M. Glazer (1997)
PNAS 94, 3122-3127
   Abstract »    Full Text »    PDF »
Defects of the Mismatch Repair Gene MSH2 Are Implicated in the Development of Murine and Human Lymphoblastic Lymphomas and Are Associated With the Aberrant Expression of Rhombotin-2 (Lmo-2) and Tal-1 (SCL).
R. Lowsky, J. F. DeCoteau, A. H. Reitmair, R. Ichinohasama, W.-F. Dong, Y. Xu, T. W. Mak, M. E. Kadin, and M. D. Minden (1997)
Blood 89, 2276-2282
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DNA methylation and genetic instability in colorectal cancer cells.
C. Lengauer, K. W. Kinzler, and B. Vogelstein (1997)
PNAS 94, 2545-2550
   Abstract »    Full Text »    PDF »
hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6.
S. Acharya, T. Wilson, S. Gradia, M. F. Kane, S. Guerrette, G. T. Marsischky, R. Kolodner, and R. Fishel (1996)
PNAS 93, 13629-13634
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Evidence for Involvement of Yeast Proliferating Cell Nuclear Antigen in DNA Mismatch Repair.
R. E. Johnson, G. K. Kovvali, S. N. Guzder, N. S. Amin, C. Holm, Y. Habraken, P. Sung, L. Prakash, and S. Prakash (1996)
J. Biol. Chem. 271, 27987-27990
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Cisplatin and Adriamycin Resistance Are Associated with MutLalpha and Mismatch Repair Deficiency in an Ovarian Tumor Cell Line.
J. T. Drummond, A. Anthoney, R. Brown, and P. Modrich (1996)
J. Biol. Chem. 271, 19645-19648
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Biochemistry and genetics of eukaryotic mismatch repair..
R Kolodner (1996)
Genes & Dev. 10, 1433-1442
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Requirement of the Yeast MSH3 and MSH6 Genes for MSH2-dependent Genomic Stability.
R. E. Johnson, G. K. Kovvali, L. Prakash, and S. Prakash (1996)
J. Biol. Chem. 271, 7285-7288
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Identification and Characterization of a Thermostable MutS Homolog from Thermus aquaticus.
I. Biswas and P. Hsieh (1996)
J. Biol. Chem. 271, 5040-5048
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Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair..
G T Marsischky, N Filosi, M F Kane, and R Kolodner (1996)
Genes & Dev. 10, 407-420
   Abstract »    PDF »
hMSH2-independent DNA Mismatch Recognition by Human Proteins.
N. E. O'Regan, P. Branch, P. Macpherson, and P. Karran (1996)
J. Biol. Chem. 271, 1789-1796
   Abstract »    Full Text »    PDF »
Appropriate partners make good matches.
P Karran (1995)
Science 268, 1857-1858
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Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells.
J. Drummond, G. Li, M. Longley, and P Modrich (1995)
Science 268, 1909-1912
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Nuclear Translocation of Mismatch Repair Proteins MSH2 and MSH6 as a Response of Cells to Alkylating Agents.
M. Christmann and B. Kaina (2000)
J. Biol. Chem. 275, 36256-36262
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From the Cover: Carcinogen-specific induction of genetic instability.
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PNAS 98, 5770-5775
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Science. ISSN 0036-8075 (print), 1095-9203 (online)