MSH6

Summary

Gene Symbol: MSH6
Description: mutS homolog 6
Alias: GTBP, GTMBP, HNPCC5, HSAP, p160, DNA mismatch repair protein Msh6, G/T mismatch-binding protein, mutS protein homolog 6, mutS-alpha 160 kDa subunit, sperm-associated protein
Species: human

Top Publications

  1. ncbi Value of immunohistochemical detection of DNA mismatch repair proteins in predicting germline mutation in hereditary colorectal neoplasms
    Jinru Shia
    Department of Pathology, Memorial Sloan Kettering, Cancer Center, New York, NY 10021, USA
    Am J Surg Pathol 29:96-104. 2005
  2. ncbi Effect of exogenous MSH6 and POLD1 expression on the mutation rate of the HPRT locus in a human colon cancer cell line with mutator phenotype, DLD-1
    Tomonori Yabuta
    Biology Division, National Cancer Center Research Institute, Tokyo 104 0045, Japan
    Int J Oncol 24:697-702. 2004
  3. ncbi Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients
    Heather Hampel
    Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center, 420 West 12th Avenue, Columbus, OH 43210, USA
    Cancer Res 66:7810-7. 2006
  4. doi Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations
    E Barrow
    Department of General Surgery, Manchester Royal Infirmary, Manchester, UK
    Clin Genet 75:141-9. 2009
  5. ncbi Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells
    J T Drummond
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Science 268:1909-12. 1995
  6. ncbi Mutations of GTBP in genetically unstable cells
    N Papadopoulos
    Johns Hopkins Oncology Center, Baltimore, MD 21231, USA
    Science 268:1915-7. 1995
  7. ncbi Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair
    J I Risinger
    Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Nat Genet 14:102-5. 1996
  8. pmc hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6
    S Acharya
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Proc Natl Acad Sci U S A 93:13629-34. 1996
  9. ncbi Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer
    M Miyaki
    Nat Genet 17:271-2. 1997
  10. ncbi The human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch
    S Gradia
    Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Cell 91:995-1005. 1997

Research Grants

  1. Repair of Oxidatively Damaged Guanines
    A LIEN L LU-CHANG; Fiscal Year: 2013
  2. NEW HUMAN DNA REPAIR ENDONUCLEASE
    Alfonso Bellacosa; Fiscal Year: 2002
  3. Mismatch repair in V region mutation and isotype switching
    Matthew D Scharff; Fiscal Year: 2013
  4. Sapna Syngal; Fiscal Year: 2016
  5. Mechanistic studies of DNA repair and damage response
    Dorothy A Erie; Fiscal Year: 2010
  6. PCNA clamp mechanisms in DNA replication and repair
    Manju M Hingorani; Fiscal Year: 2010
  7. Polly A Newcomb; Fiscal Year: 2014
  8. Toward a molecular classification of human gliomas
    David N Louis; Fiscal Year: 2013
  9. Screening Pretest for HNPCC
    Jeremy Fields; Fiscal Year: 2007
  10. SEAN VAHRAM TAVTIGIAN; Fiscal Year: 2016

Detail Information

Publications201 found, 100 shown here

  1. ncbi Value of immunohistochemical detection of DNA mismatch repair proteins in predicting germline mutation in hereditary colorectal neoplasms
    Jinru Shia
    Department of Pathology, Memorial Sloan Kettering, Cancer Center, New York, NY 10021, USA
    Am J Surg Pathol 29:96-104. 2005
    ..of IHC versus that of microsatellite instability (MSI) testing in predicting mutation status of the MLH1, MSH2, and MSH6 genes in colorectal carcinomas and adenomas, and explored the frequency and significance of immunohistochemical ..
  2. ncbi Effect of exogenous MSH6 and POLD1 expression on the mutation rate of the HPRT locus in a human colon cancer cell line with mutator phenotype, DLD-1
    Tomonori Yabuta
    Biology Division, National Cancer Center Research Institute, Tokyo 104 0045, Japan
    Int J Oncol 24:697-702. 2004
    ..Since DLD-1 carries frameshift mutations in both alleles of the MSH6 gene and missense mutations in the POLD1 gene, either or both of these mutations were suggested to be involved in ..
  3. ncbi Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients
    Heather Hampel
    Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center, 420 West 12th Avenue, Columbus, OH 43210, USA
    Cancer Res 66:7810-7. 2006
    ..Patients with MSI-positive tumors underwent testing for germ line mutations in MLH1, MSH2, MSH6, and PMS2. Of 543 tumors studied, 118 (21.7%) were MSI positive (98 of 118 MSI high and 20 of 118 MSI low)...
  4. doi Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations
    E Barrow
    Department of General Surgery, Manchester Royal Infirmary, Manchester, UK
    Clin Genet 75:141-9. 2009
    ..0003). Gastric cancer risk in those born after 1935 does not justify surveillance. These penetrance estimates have been corrected for ascertainment bias and are appropriate for those referred to a high-risk clinic...
  5. ncbi Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells
    J T Drummond
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Science 268:1909-12. 1995
    ....
  6. ncbi Mutations of GTBP in genetically unstable cells
    N Papadopoulos
    Johns Hopkins Oncology Center, Baltimore, MD 21231, USA
    Science 268:1915-7. 1995
    ..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 ..
  7. ncbi Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair
    J I Risinger
    Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Nat Genet 14:102-5. 1996
    ..A subsequent search revealed a second gene mutation in HHUA cells, a missense mutation in the MSH6 gene...
  8. pmc hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6
    S Acharya
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Proc Natl Acad Sci U S A 93:13629-34. 1996
    ..proteins, similar to protein complexes demonstrated by studies of the Saccharomyces cerevisiae MSH2, MSH3, and MSH6. hMSH2 was also found to form a homomultimer complex, but neither hMSH3 nor hMSH6 appear to interact with ..
  9. ncbi Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer
    M Miyaki
    Nat Genet 17:271-2. 1997
  10. ncbi The human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch
    S Gradia
    Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Cell 91:995-1005. 1997
    ..These results suggest a new model for the function of MutS proteins during mismatch repair in which the switch determines the timing of downstream events...
  11. pmc Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of mutations found in hereditary nonpolyposis colorectal cancer
    S Guerrette
    Genetics and Molecular Biology Program, Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Mol Cell Biol 18:6616-23. 1998
    ..These data support the notion that these HNPCC-associated mutations may affect some other function of the heterodimeric complexes than simply the static interaction of hMSH2 with hMSH3 or hMSH2 with hMSH6...
  12. ncbi Familial endometrial cancer in female carriers of MSH6 germline mutations
    J Wijnen
    Nat Genet 23:142-4. 1999
  13. pmc Association of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations
    Y Wu
    Departments of Medical Genetics, University of Groningen, Groningen, The Netherlands
    Am J Hum Genet 65:1291-8. 1999
    ..Correction of base-base mismatches is the major function of MSH6. Since mismatches present with an MSI-low phenotype, we assumed that the phenotype in patients with HNPCC-related ..
  14. pmc BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures
    Y Wang
    Verna and Mars McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Genes Dev 14:927-39. 2000
    ..This complex includes tumor suppressors and DNA damage repair proteins MSH2, MSH6, MLH1, ATM, BLM, and the RAD50-MRE11-NBS1 protein complex...
  15. ncbi Identification of factors interacting with hMSH2 in the fetal liver utilizing the yeast two-hybrid system. In vivo interaction through the C-terminal domains of hEXO1 and hMSH2 and comparative expression analysis
    L J Rasmussen
    Department of Life Sciences and Chemistry, Roskilde University, DK 4000, Roskilde, Denmark
    Mutat Res 460:41-52. 2000
    ..Northern blot analysis also revealed that hEXO1/HEX1 is highly expressed in several liver cancer cell lines as well as in colon and pancreas adenocarcinomas, but not in the corresponding non-neoplastic tissue...
  16. ncbi Nuclear translocation of mismatch repair proteins MSH2 and MSH6 as a response of cells to alkylating agents
    M Christmann
    Division of Applied Toxicology, Institute of Toxicology, University of Mainz, Obere Zahlbacher Strasse 67, D 55131 Mainz, Germany
    J Biol Chem 275:36256-62. 2000
    ..in DNA, such as N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea, elevates the level of MSH2 and MSH6 and increases GT mismatch binding activity in the nucleus...
  17. pmc hMSH3 and hMSH6 interact with PCNA and colocalize with it to replication foci
    H E Kleczkowska
    Institute of Medical Radiobiology of the University of Zurich and the Paul Scherrer Institute, Ch 8008 Zurich, Switzerland
    Genes Dev 15:724-36. 2001
    ..We postulate that PCNA plays a role in repair initiation by guiding the mismatch repair proteins to free termini in the newly replicated DNA strands...
  18. pmc Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch pedigree
    A Wagner
    Department of Clinical Genetics, Erasmus University Rotterdam, The Netherlands
    J Med Genet 38:318-22. 2001
    ..Recently, mutations in another MMR gene, MSH6 (also known as GTBP), have also been shown to result in HNPCC...
  19. ncbi Involvement of hMSH6 in the development of hereditary and sporadic colorectal cancer revealed by immunostaining is based on germline mutations, but rarely on somatic inactivation
    Jens Plaschke
    Department of Surgical Research, Carl Gustav Carus Klinikum, Technical University, Dresden, Germany
    Int J Cancer 97:643-8. 2002
    ..We conclude that the involvement of somatic or epigenetic hMSH6 inactivation in colorectal cancer is rare...
  20. ncbi Functional analysis of MSH6 mutations linked to kindreds with putative hereditary non-polyposis colorectal cancer syndrome
    Reetta Kariola
    Department of Biosciences, Division of Genetics, University of Helsinki, FIN 00014 Helsinki, Finland
    Hum Mol Genet 11:1303-10. 2002
    To date, five mismatch-repair (MMR) genes, MLH1, MSH2, MSH6, MSH3 and PMS2, are known to be involved in human MMR function...
  21. ncbi Two mismatch repair gene mutations found in a colon cancer patient--which one is pathogenic?
    Reetta Kariola
    Department of Biosciences, Division of Genetics, University of Helsinki, Viikinkaari 5, 00014 Helsinki, Finland
    Hum Genet 112:105-9. 2003
    ..Germline mutations in five different mismatch repair (MMR) genes, MSH2, MSH6, MLH1, MLH3, and PMS2 are linked to HNPCC...
  22. pmc Prevalence of defective DNA mismatch repair and MSH6 mutation in an unselected series of endometrial cancers
    Paul J Goodfellow
    Department of Surgery, Washington University School of Medicine, Campus Box 8109, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 100:5908-13. 2003
    ..Sporadic endometrial cancers also exhibit MSI, usually associated with methylation of the MLH1 promoter. Germ-line MSH6 mutations, which are rare in HNPCC, have been reported in several families with multiple members affected with ..
  23. pmc Genomic rearrangements of hMSH6 contribute to the genetic predisposition in suspected hereditary non-polyposis colorectal cancer syndrome
    J Plaschke
    Department of Surgical Research, Carl Gustav Carus Klinikum, Dresden University of Technology, D 01307 Dresden, Germany
    J Med Genet 40:597-600. 2003
    ..A substantial fraction of these mutations exists in genomic rearrangements of hMSH2 and hMLH1. In contrast, genomic rearrangements have not been reported in hMSH6...
  24. ncbi The Bloom's syndrome helicase interacts directly with the human DNA mismatch repair protein hMSH6
    Graziella Pedrazzi
    Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstr 190, CH 8057 Zurich, Switzerland
    Biol Chem 384:1155-64. 2003
    ....
  25. ncbi MSH6 germline mutations are rare in colorectal cancer families
    Paolo Peterlongo
    Cell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Int J Cancer 107:571-9. 2003
    Germline mutations in MSH6 can cause HNPCC, which is associated with a tumor phenotype featuring MSI. However, tumors arising in persons with disease-causing mutations of MSH6 may or may not exhibit MSI...
  26. ncbi Toward new strategies to select young endometrial cancer patients for mismatch repair gene mutation analysis
    Maran J W Berends
    Department of Gynaecology, University Hospital Groningen, Hanzeplein 1, PO Box 30 001, 9700 RB Groningen, The Netherlands
    J Clin Oncol 21:4364-70. 2003
    ....
  27. pmc MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation
    Yi Wang
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 100:15387-92. 2003
    ..These data support a model in which MSH2 and ATR function upstream to regulate two branches of the response pathway to DNA damage caused by MNNG...
  28. ncbi The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase
    Qin Yang
    Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bldg 37, Rm 3068, 37 Convent Drive, Bethesda, MD 20892 4255, USA
    Oncogene 23:3749-56. 2004
    ..These data suggest that hMSH2/6 formed a complex with BLM-p53-RAD51 in response to the damaged DNA forks during double-stranded break repair...
  29. ncbi A defined human system that supports bidirectional mismatch-provoked excision
    Leonid Dzantiev
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Mol Cell 15:31-41. 2004
    ..By contrast, RFC and PCNA have only a limited effect on 5' to 3' excision directed by a 5' strand break...
  30. ncbi MutSalpha binds to and promotes synapsis of transcriptionally activated immunoglobulin switch regions
    Erik D Larson
    Department of Immunology, Molecular and Cellular Biology Graduate Program, University of Washington School of Medicine, 1959 N E Pacific Street, Box 357650, Seattle, WA 98195, USA
    Curr Biol 15:470-4. 2005
    ..deaminase, AID, and conserved DNA repair factors, including the mismatch repair heterodimer, MutSalpha (MSH2/MSH6)...
  31. ncbi Use of molecular tumor characteristics to prioritize mismatch repair gene testing in early-onset colorectal cancer
    Melissa C Southey
    Genetic Epidemiology Laboratory, Department of Pathology, Australia
    J Clin Oncol 23:6524-32. 2005
    ..The relationships between mismatch repair (MMR) protein expression, microsatellite instability (MSI), family history, and germline MMR gene mutation status have not been studied on a population basis...
  32. ncbi High frequency of hereditary colorectal cancer in Newfoundland likely involves novel susceptibility genes
    Michael O Woods
    Discipline of Genetics, Department of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John s, Newfoundland, Canada
    Clin Cancer Res 11:6853-61. 2005
    ..Our purpose was to determine the proportion of hereditary colorectal cancer and to determine the genetic basis of disease in both population and clinically referred cohorts from Newfoundland...
  33. ncbi MUTYH and the mismatch repair system: partners in crime?
    Renée C Niessen
    Department of Medical Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Hum Genet 119:206-11. 2006
    ..5%). In group II five monoallelic germline MUTYH mutations were found (14%), four of them in MSH6 missense mutation carriers (20%)...
  34. pmc Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer
    R C Niessen
    Department of Gastroenterology, University Medical Center Groningen, 9700 RB Groningen, The Netherlands
    Gut 55:1781-8. 2006
    ..Patients with early-onset colorectal cancer (CRC) or those with multiple tumours associated with hereditary non-polyposis colorectal cancer (HNPCC) raise suspicion of the presence of germline DNA mismatch repair (MMR) gene mutations...
  35. ncbi Frequency of hereditary non-polyposis colorectal cancer among unselected patients with colorectal cancer in Germany
    C Lamberti
    Department of Internal Medicine I, University of Bonn, Bonn, Germany
    Digestion 74:58-67. 2006
    ..This project aims at estimating the proportion of HNPCC among unselected patients with CRC...
  36. ncbi Lynch syndrome (hereditary nonpolyposis colorectal cancer) diagnostics
    Kristina Lagerstedt Robinson
    Department of Clinical Genetics, Karolinska University Hospital, S 17176 Stockholm, Sweden
    J Natl Cancer Inst 99:291-9. 2007
    ..The syndrome is explained by germline mutations in DNA mismatch repair (MMR) genes, and there is a need for diagnostic tools to preselect patients for genetic testing to diagnose those with HNPCC...
  37. ncbi Frequency of constitutional MSH6 mutations in a consecutive series of families with clinical suspicion of HNPCC
    B Roncari
    Department of Medicine and Medical Specialties, University of Modena and Reggio Emilia, Modena, Italy
    Clin Genet 72:230-7. 2007
    ..In a lower fraction of cases, another gene of the mismatch repair (MMR) machinery, MSH6, may be responsible...
  38. pmc Recently identified colon cancer predispositions: MYH and MSH6 mutations
    Fay Kastrinos
    Division of Gastroenterology, Brigham and Women s Hospital, Boston, MA, USA
    Semin Oncol 34:418-24. 2007
    ..Most recently, MYH-associated polyposis (MAP) and an "atypical Lynch syndrome" related to the presence of MSH6 mutations have been linked to an increased risk of CRC...
  39. ncbi RNA-based mutation analysis identifies an unusual MSH6 splicing defect and circumvents PMS2 pseudogene interference
    J Etzler
    Department of Medical Genetics, Medical University Vienna, Vienna, Austria
    Hum Mutat 29:299-305. 2008
    Heterozygous germline mutations in one of the mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 cause hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome, a dominantly inherited cancer susceptibility syndrome...
  40. pmc Germline MSH6 mutations are more prevalent in endometrial cancer patient cohorts than hereditary non polyposis colorectal cancer cohorts
    Lisa A Devlin
    Department of Medical Genetics, Belfast City Hospital, Belfast HSC Trust, Belfast BT9 7AB, United Kingdom
    Ulster Med J 77:25-30. 2008
    To determine and compare the prevalence of MSH6 (a mismatch repair gene) mutations in a cohort of families with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), and in an unselected cohort of endometrial cancer patients (EC).
  41. doi Human mismatch repair protein MSH6 contains a PWWP domain that targets double stranded DNA
    Cedric Laguri
    CEA Laboratoire de Biologie Structurale et Radiobiologie, iBiTec Saclay, 91191 Gif sur Yvette, France
    Biochemistry 47:6199-207. 2008
    The eukaryotic mismatch repair (MMR) protein MSH6 exhibits a core region structurally and functionally similar to bacterial MutS...
  42. doi Colorectal cancer in HNPCC: cumulative lifetime incidence, survival and tumour distribution. A report of 121 families with proven mutations
    E Barrow
    Department of General Surgery, Manchester Royal Infirmary, Manchester, UK
    Clin Genet 74:233-42. 2008
    ..Current colonoscopic screening guidelines are appropriate...
  43. doi Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population
    Mef Nilbert
    Clinical Research Centre and HNPCC Register, Copenhagen University, Hvidovre University Hospital, Kettegard Alle 30, Hvidovre, 2650, Denmark
    Fam Cancer 8:75-83. 2009
    ..The different MMR genes contribute to 40% (MSH2), 29% (MLH1), and 22% (MSH6) of the mutations and the Danish population thus shows a considerably higher frequency of MSH6 mutations than ..
  44. doi A high incidence of MSH6 mutations in Amsterdam criteria II-negative families tested in a diagnostic setting
    D Ramsoekh
    Erasmus MC University Medical Center, s Gravendijkwal 230, 3015CE Rotterdam, The Netherlands
    Gut 57:1539-44. 2008
    In Lynch syndrome, the clinical phenotype in MSH6 mutation families differs from that in MLH1 and MSH2 families...
  45. pmc Hereditary cancer-associated missense mutations in hMSH6 uncouple ATP hydrolysis from DNA mismatch binding
    Jennifer L Cyr
    Neag Comprehensive Cancer Center, University of Connecticut Health Center, Farmington, Connecticut 06030, USA
    J Biol Chem 283:31641-8. 2008
    ....
  46. pmc The nucleotide binding dynamics of human MSH2-MSH3 are lesion dependent
    Barbara A L Owen
    Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    Nat Struct Mol Biol 16:550-7. 2009
    ..that the human DNA mismatch complex MSH2-MSH3 recognizes small loops by a mechanism different from that of MSH2-MSH6 for single-base mismatches. The subunits MSH2 and MSH3 can bind either ADP or ATP with similar affinities...
  47. doi Meta-analysis of MSH6 gene mutation frequency in colorectal and endometrial cancers
    Ya shuang Zhao
    Department of Epidemiology, Public Health College, Harbin Medical University, Heilongjiang Province, People s Republic of China
    J Toxicol Environ Health A 72:690-7. 2009
    Studies on mutations and mutation frequencies of the MSH6 gene, which mainly focus on new types of mutations in small samples, have been published ever since the first report of MSH6 mutation in two atypical hereditary non-polyposis ..
  48. pmc Calculation of risk of colorectal and endometrial cancer among patients with Lynch syndrome
    Elena Stoffel
    Brigham and Women s Hospital, Boston, Massachusetts Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Gastroenterology 137:1621-7. 2009
    ..Some previous estimates of lifetime risk for CRC and endometrial cancer (EC) did not control for ascertainment and were susceptible to bias toward overestimated risk...
  49. pmc Constitutional mismatch repair deficiency and childhood leukemia/lymphoma--report on a novel biallelic MSH6 mutation
    Tim Ripperger
    Institute of Cell and Molecular Pathology, Hannover Medical School, Carl Neuberg Str 1, 30625 Hannover, Germany
    Haematologica 95:841-4. 2010
    ..We report on a case with constitutional mismatch repair deficiency caused by a novel MSH6 mutation leading to a T-cell lymphoma and colonic adenocarcinoma at six and 13 years of age, respectively...
  50. pmc Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different risk profiles may influence clinical management
    Dewkoemar Ramsoekh
    Department of Gastroenterology and Hepatology Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands
    Hered Cancer Clin Pract 7:17. 2009
    ..The risk is dependent of the affected mismatch repair gene. The aim of the present study was to calculate the cumulative risk of LS related cancers in proven MLH1, MSH2 and MSH6 mutation carriers.
  51. pmc Risks of Lynch syndrome cancers for MSH6 mutation carriers
    Laura Baglietto
    Cancer Epidemiology Centre, Victorian Cancer Registry, Carlton, Victoria, Australia
    J Natl Cancer Inst 102:193-201. 2010
    Germline mutations in MSH6 account for 10%-20% of Lynch syndrome colorectal cancers caused by hereditary DNA mismatch repair gene mutations. Because there have been only a few studies of mutation carriers, their cancer risks are uncertain.
  52. pmc MutSbeta exceeds MutSalpha in dinucleotide loop repair
    J Kantelinen
    Department of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 5, Helsinki, Finland
    Br J Cancer 102:1068-73. 2010
    The target substrates of DNA mismatch recognising factors MutSalpha (MSH2+MSH6) and MutSbeta (MSH2+MSH3) have already been widely researched. However, the extent of their functional redundancy and clinical substance remains unclear...
  53. pmc MSH6 and MUTYH deficiency is a frequent event in early-onset colorectal cancer
    María Dolores Giráldez
    Gastroenterology Department, Institut de Malalties Digestives i Metaboliques, Hospital Clinic, Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas CIBERehd, Institut d Investigacions Biomediques August Pi i Sunyer, DIBAPS, University of Barcelona, Barcelona, Spain
    Clin Cancer Res 16:5402-13. 2010
    ..Lynch syndrome is the most frequent CRC hereditary cause. The MUTYH gene has also been related to hereditary CRC. A systematic characterization of these two diseases has not been reported previously in this population...
  54. pmc Tumours with loss of MSH6 expression are MSI-H when screened with a pentaplex of five mononucleotide repeats
    J F You
    INSERM, UMRS 938 Centre de Recherche Saint Antoine, Equipe Instabilité des Microsatellites et Cancers, 184 rue du Faubourg Saint Antoine, Paris F 75012, France
    Br J Cancer 103:1840-5. 2010
    ..are characterised by alterations in one of the four major proteins of the mismatch repair (MMR) system (MLH1, MSH2, MSH6 or PMS2) that renders them MMR deficient, whereas MSI-L and MSS tumours are generally MMR proficient...
  55. doi Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome
    Valerie Bonadona
    Universite Lyon 1, Centre National de la Recherche Scientifique UMR5558, Villeurbanne, Centre Leon Berard, Lyon, Cedex 08, France
    JAMA 305:2304-10. 2011
    ..Providing accurate estimates of cancer risks is a major challenge in the clinical management of Lynch syndrome...
  56. doi The hMsh2-hMsh6 complex acts in concert with monoubiquitinated PCNA and Pol η in response to oxidative DNA damage in human cells
    Anastasia Zlatanou
    Group TLS Polymerases and Cancer, Universite Paris Sud, CNRS UMR8200, Institut Gustave Roussy, 94800 Villejuif, France
    Mol Cell 43:649-62. 2011
    ....
  57. pmc Mismatch repair genes expression defects & association with clinicopathological characteristics in colorectal carcinoma
    Gurjeet Kaur
    Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Malaysia
    Indian J Med Res 134:186-92. 2011
    ..This study was aimed to determine the frequency of abnormal MMR gene protein expression in colorectal carcinoma in Northern Peninsular Malaysia using immunohistochemistry...
  58. pmc Interplay between mismatch repair and chromatin assembly
    Barbara Schöpf
    Institute of Molecular Cancer Research, University of Zurich, Winterthurerstasse 190, CH 8057 Zurich, Switzerland
    Proc Natl Acad Sci U S A 109:1895-900. 2012
    ..the processivity factor of replicative DNA polymerases, which is loaded at DNA termini and which interacts with the MSH6 subunit of the mismatch recognition factor MutSα, as well as with CAF-1...
  59. pmc Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study
    Aung Ko Win
    The University of Melbourne, Australia
    J Clin Oncol 30:958-64. 2012
    ..To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population...
  60. pmc Proliferating cell nuclear antigen (PCNA)-binding protein C1orf124 is a regulator of translesion synthesis
    Gargi Ghosal
    Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 287:34225-33. 2012
    ..Thus, C1orf124 acts at multiple steps in TLS, stabilizes RAD18 and ubiquitinated PCNA at damage sites, and facilitates the switch from replicative to TLS polymerase to bypass DNA lesion...
  61. ncbi Germ-line msh6 mutations in colorectal cancer families
    R D Kolodner
    Ludwig Institute for Cancer Research, Department of Medicine and Cancer Center, University of California San Diego Medical School, La Jolla 92093 0660, USA
    Cancer Res 59:5068-74. 1999
    ..We examined the frequency of germ-line msh6 mutations in a population-based series of 140 colorectal cancer patients, including 45 sporadic cases, 91 familial ..
  62. ncbi Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1
    Q Wang
    Department of Pathology and Laboratory Medicine, The Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, PA 19104, USA
    Oncogene 20:4640-9. 2001
    ..The functional interaction between BRCA1 and hMSH2 may provide a partial explanation for the background of gynecological and colorectal cancer in both HNPCC and BRCA1 kindreds, respectively...
  63. pmc Molecular and clinical characteristics of MSH6 variants: an analysis of 25 index carriers of a germline variant
    Maran J W Berends
    Department of Gastroenterology, University Hospital Groningen, Groningen, The Netherlands
    Am J Hum Genet 70:26-37. 2002
    The MSH6 gene is one of the mismatch-repair genes involved in hereditary nonpolyposis colorectal cancer (HNPCC). Three hundred sixteen individuals who were known or suspected to have HNPCC were analyzed for MSH6 germline mutations...
  64. pmc The MutSalpha-proliferating cell nuclear antigen interaction in human DNA mismatch repair
    Ravi R Iyer
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 283:13310-9. 2008
    ....
  65. ncbi MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families
    H F Vasen
    Netherlands Foundation for the Detection of Hereditary Tumors, Leiden University Medical Centre
    J Clin Oncol 19:4074-80. 2001
    ..The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and MSH6. The aims of the present study were to compare the risk of developing colorectal, endometrial, and other cancers ..
  66. pmc MLH1 promoter germline-methylation in selected probands of Chinese hereditary non-polyposis colorectal cancer families
    Heng Hua Zhou
    Department of Pathology, Cancer Hospital, Fudan University, Shanghai 200032, China
    World J Gastroenterol 14:7329-34. 2008
    ..To detect the MLH1 gene promoter germline-methylation in probands of Chinese hereditary nonpolyposis colorectal cancer (HNPCC), and to evaluate the role of methylation in MLH1 gene promoter and molecular genetics in screening for HNPCC...
  67. ncbi [Study on the germline mutation of MSH6 gene in Chinese hereditary nonpolyposis colorectal cancer pedigrees using PCR based sequencing]
    Shi yan Yan
    Department of Pathology, Cancer Hospital, Fudan University, Shanghai, 200032 PR China
    Zhonghua Yi Xue Yi Chuan Xue Za Zhi 24:640-5. 2007
    To detect the germline mutation of mismatch repair gene (MSH6) in hereditary nonpolyposis colorectal cancer (HNPCC) kindreds fulfilling different clinical criteria.
  68. ncbi Somatic frameshift alterations in mononucleotide repeat-containing genes in different tumor types from an HNPCC family with germline MSH2 mutation
    M Planck
    Department of Oncology, University Hospital, Lund, Sweden
    Genes Chromosomes Cancer 29:33-9. 2000
    ..g., TGFBRII, BAX, IGFIIR, TCF4, MSH3, and MSH6. We have studied the occurrence of somatic frameshift alterations in these mononucleotide repeat-containing genes ..
  69. ncbi Prospective determination of prevalence of lynch syndrome in young women with endometrial cancer
    Karen H Lu
    Department of Gynecologic Oncology, Division of Surgery, The University of Texas M D Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030 4009, USA
    J Clin Oncol 25:5158-64. 2007
    ..The purpose of this study was to determine the prevalence of MLH1, MSH2, and MSH6 mutations in an unselected cohort of women diagnosed with endometrial cancer at age younger than 50 years.
  70. ncbi A lack of DNA mismatch repair on an athymic murine background predisposes to hematologic malignancy
    Marcia R Campbell
    Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
    Cancer Res 65:2626-35. 2005
    ..Here, we bred Msh2- and Msh6-deficient mice to athymic nude mice, hypothesizing that a broader tumor spectrum may be observed if mice are able ..
  71. pmc First report of a de novo germline mutation in the MLH1 gene
    Rein P Stulp
    Department of Clinical Genetics, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands
    World J Gastroenterol 12:809-11. 2006
    ..Germline mutations in the DNA mismatch repair (MMR) genes, particularly MLH1, MSH2, and MSH6, underlie this disorder...
  72. pmc Patients with an unexplained microsatellite instable tumour have a low risk of familial cancer
    L I H Overbeek
    Department of Human Genetics 849, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
    Br J Cancer 96:1605-12. 2007
    ..were analysed for microsatellite instability, MLH1 promoter methylation and/or germline mutations in MLH1, MSH2, MSH6, and PMS2...
  73. pmc The Saccharomyces cerevisiae Msh2 and Msh6 proteins form a complex that specifically binds to duplex oligonucleotides containing mismatched DNA base pairs
    E Alani
    Section of Genetics and Development, Cornell University, Ithaca, New York 14853 2703, USA
    Mol Cell Biol 16:5604-15. 1996
    ..In this study, the S. cerevisiae 109-kDa Msh2 and 140-kDa Msh6 proteins were cooverexpressed in S...
  74. pmc Mismatch recognition-coupled stabilization of Msh2-Msh6 in an ATP-bound state at the initiation of DNA repair
    Edwin Antony
    Wesleyan University, Molecular Biology and Biochemistry Department, 205 Hall Atwater Laboratories, Middletown, Connecticut 06459, USA
    Biochemistry 42:7682-93. 2003
    Mismatch repair proteins correct errors in DNA via an ATP-driven process. In eukaryotes, the Msh2-Msh6 complex recognizes base pair mismatches and small insertion/deletions in DNA and initiates repair...
  75. pmc Mechanism of cadmium-mediated inhibition of Msh2-Msh6 function in DNA mismatch repair
    Markus Wieland
    Molecular Biology and Biochemistry Department, Wesleyan University, Middletown Connecticut 06459, USA
    Biochemistry 48:9492-502. 2009
    The observation that Cadmium (Cd(2+)) inhibits Msh2-Msh6, which is responsible for identifying base pair mismatches and other discrepancies in DNA, has led to the proposal that selective targeting of this protein and consequent ..
  76. pmc The role of mismatch repair in the prevention of base pair mutations in Saccharomyces cerevisiae
    M C Earley
    Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, GA 30322, USA
    Proc Natl Acad Sci U S A 95:15487-91. 1998
    ..In Saccharomyces cerevisiae, the products of three genes homologous to Escherichia coli mutS-MSH2, MSH3, and MSH6-function in MMR by recognizing mispaired bases...
  77. ncbi A mutation in the MSH6 subunit of the Saccharomyces cerevisiae MSH2-MSH6 complex disrupts mismatch recognition
    J Bowers
    Section of Genetics and Development, Cornell University, Ithaca, New York 14853 2703, USA
    J Biol Chem 274:16115-25. 1999
    In yeast, MSH2 interacts with MSH6 to repair base pair mismatches and single nucleotide insertion/deletion mismatches and with MSH3 to recognize small loop insertion/deletion mismatches...
  78. pmc EXO1 and MSH6 are high-copy suppressors of conditional mutations in the MSH2 mismatch repair gene of Saccharomyces cerevisiae
    T Sokolsky
    Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853 2703, USA
    Genetics 155:589-99. 2000
    ..inviability of two mutants, msh2-L560S pol3-01 and msh2-L910P pol3-01, was suppressed by overexpression of EXO1 and MSH6, respectively...
  79. ncbi Heat-stable alkaline phosphatase. A putative tumor marker of head and neck squamous cell carcinoma
    M B Rassam
    Department of Chemistry and Biochemistry, Saddam College of Medicine, Baghdad, Iraq
    Acta Oncol 34:49-52. 1995
    Serum total alkaline phosphatase (AP) activity and heat-stable AP (HSAP) were investigated in patients with uncontrolled squamous cell carcinoma of the head and neck before and after treatment...
  80. pmc Alkylation damage causes MMR-dependent chromosomal instability in vertebrate embryos
    Harma Feitsma
    Hubrecht Institute, Royal Academy of Arts and Sciences and University Medical Centre Utrecht, Cancer Genomics Center, 3584 CT, Utrecht, The Netherlands
    Nucleic Acids Res 36:4047-56. 2008
    ..Consistent with the damage-sensing role of the MMR system, mutant embryos lacking the MMR enzyme MSH6 displayed lower lethality than wild-type embryos after exposure to ENU and MNU...
  81. pmc Fibroblast growth factor-1 stimulation of quiescent NIH 3T3 cells increases G/T mismatch-binding protein expression
    P J Donohue
    Department of Molecular Biology, Holland Laboratory, American Red Cross, Rockville, MD 20855, USA
    Biochem J 319:9-12. 1996
    ..report that one of these genes, called FGF-regulated (FR)-3, is predicted to encode G/T mismatch-binding protein (GTBP), a component of the mammalian DNA mismatch correction system...
  82. ncbi Somatic expansion behaviour of the (CTG)n repeat in myotonic dystrophy knock-in mice is differentially affected by Msh3 and Msh6 mismatch-repair proteins
    Walther J A A van den Broek
    Department of Cell Biology, UMC Nijmegen, Nijmegen Center for Molecular Life Sciences, PO Box 9101, 6500 HB Nijmegen, The Netherlands
    Hum Mol Genet 11:191-8. 2002
    ..In contrast, Msh6 deficiency resulted in a significant increase in the frequency of somatic expansions...
  83. pmc Temozolomide- and fotemustine-induced apoptosis in human malignant melanoma cells: response related to MGMT, MMR, DSBs, and p53
    S C Naumann
    Department of Toxicology, University of Mainz, Mainz, Germany
    Br J Cancer 100:322-33. 2009
    ..This was related to an impaired expression of MSH2 and MSH6. The cells were not cross-resistant to fotemustine...
  84. ncbi Purification and characterization of prolyl endopeptidase from the Pacific herring, Clupea pallasi, and its role in the activation of sperm motility
    K Yoshida
    Misaki Marine Biological Station, Graduate School of Science, University of Tokyo, Kanagawa, Japan
    Dev Growth Differ 41:217-25. 1999
    ..The enzyme activities increased in the presence of herring sperm-activating protein (HSAP). Among them a prolyl endopeptidase [EC. 3. 4. 21. 26] was purified to near homogeneity from herring testis...
  85. ncbi Analysis of mismatch repair defects in the familial occurrence of lymphoma and colorectal cancer
    J Teruya-Feldstein
    Department of Pathology, Memorial Sloan Kettering Cancer Center, Memorial Hospital, New York, NY 10021, USA
    Leuk Lymphoma 43:1619-26. 2002
    ..These MMR genes include MLH1, MSH2, MSH3, MSH6, PMS1 and PMS2...
  86. ncbi Medulloblastoma, acute myelocytic leukemia and colonic carcinomas in a child with biallelic MSH6 mutations
    Richard H Scott
    Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Nat Clin Pract Oncol 4:130-4. 2007
    ..Staining for MLH1 and MSH2 was normal but was absent for MSH6. Direct sequencing of MSH6 was performed in the proband and both parents...
  87. ncbi Gene-related cancer spectrum in families with hereditary non-polyposis colorectal cancer (HNPCC)
    Johanne Geary
    Department of Medical Genetics, St George s University of London, Cranmer Terrace, London SW17 0RE, UK
    Fam Cancer 7:163-72. 2008
    ..colorectal cancer (HNPCC) (caused by mutations in mismatch-repair (MMR) genes MSH2 (n = 64), MLH1 (n = 62) or MSH6 (n = 4)) were obtained, and incidence of cancers in those families was compared to that in the general population...
  88. ncbi Birt-Hogg-Dubé gene mutations in human endometrial carcinomas with microsatellite instability
    H Fujii
    Department of Pathology II, Juntendo University School of Medicine, Tokyo, 113 8421 Japan
    J Pathol 209:328-35. 2006
    ..The poly(G)8 tract of the BAX gene, the poly(C)8 tract of MSH6, and methylation status of hMLH1 were also assessed. Thirty-nine of 139 cases (28%) showed MSI...
  89. doi Selection of endometrial carcinomas for DNA mismatch repair protein immunohistochemistry using patient age and tumor morphology enhances detection of mismatch repair abnormalities
    Karuna Garg
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Am J Surg Pathol 33:925-33. 2009
    ..IHC abnormality in the younger group was approximately 30% with a nearly equal distribution of MLH1/PMS2 and MSH2/MSH6 abnormalities. In the older age group, TM-MMR triggered IHC analysis in 31 of 34 cases...
  90. doi Rhabdomyosarcoma in patients with constitutional mismatch-repair-deficiency syndrome
    C P Kratz
    Division of Clinical Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University Innsbruck, Schoepfstr 41, 6020 Innsbruck, Austria
    J Med Genet 46:418-20. 2009
    Biallelic germline mutations in the mismatch repair genes MLH1, MSH2, MSH6 or PMS2 cause a recessive childhood cancer syndrome characterised by early-onset malignancies and signs reminiscent of neurofibromatosis type 1 (NF1)...
  91. pmc Partial loss of heterozygosity events at the mutated gene in tumors from MLH1/MSH2 large genomic rearrangement carriers
    Katarina Zavodna
    Laboratory of Cancer Genetics, Cancer Research Institute of Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava, Slovak Republic
    BMC Cancer 9:405. 2009
    ..We sought to determine the frequency of LGRs in Slovak HNPCC patients and to study LOH in tumors from LGR carriers at the LGR region, as well as at other heterozygous markers within the gene to more precisely define conversion tracts...
  92. ncbi Ovarian cancer at young age: the contribution of mismatch-repair defects in a population-based series of epithelial ovarian cancer before age 40
    K Domanska
    Department of Oncology, Lund University Hospital, Lund, Sweden
    Int J Gynecol Cancer 17:789-93. 2007
    ..Immunostaining using antibodies against MLH1, PMS2, MSH2, and MSH6 was used to assess the mismatch-repair status and revealed loss of expression of MLH1/PMS2 in two cases, loss of ..
  93. doi Microsatellite instability and mismatch repair protein defects in ovarian epithelial neoplasms in patients 50 years of age and younger
    Kristin C Jensen
    Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Am J Surg Pathol 32:1029-37. 2008
    ..BAT26, D2S123, D5S346, and D17S250) and deficiency of MMR protein expression by immunohistochemistry (MLH1, MSH2, MSH6, and PMS2)...
  94. pmc Rapid DNA double-strand breaks resulting from processing of Cr-DNA cross-links by both MutS dimers
    Mindy F Reynolds
    Department of Pathology, Laboratory Medicine, Brown University, Providence, Rhode Island 02912, USA
    Cancer Res 69:1071-9. 2009
    ..We found that MSH2-MSH6 (MutSalpha) dimer effectively bound DNA probes containing ascorbate-Cr-DNA and cysteine-Cr-DNA cross-links...
  95. pmc Hijacked DNA repair proteins and unchained DNA polymerases
    Huseyin Saribasak
    Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Philos Trans R Soc Lond B Biol Sci 364:605-11. 2009
    ..In the mutagenic pathway, we first studied the role of mismatch repair proteins, MSH2, MSH3, MSH6, PMS2 and MLH1, since they would recognize mismatches...
  96. ncbi Molecular cloning of zebrafish (Danio rerio) MutS homolog 6(MSH6) and noncoordinate expression of MSH6 gene activity and G-T mismatch binding proteins in zebrafish larvae
    Fu Lung Yeh
    Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 20224, Taiwan, Republic of China
    J Exp Zool A Comp Exp Biol 297:118-29. 2003
    Eukaryotic MutS homolog 6(MSH6) is a DNA mismatch recognition protein associated with mismatch repair of simple base-base mispairs and small insertion-deletion loops...
  97. ncbi Genomic rearrangements in MSH2, MLH1 or MSH6 are rare in HNPCC patients carrying point mutations
    Steffen Pistorius
    Department of Visceral, Thoracic and Vascular Surgery, Technische Universitat Dresden, Fetscherstr 74, 01307 Dresden, Germany
    Cancer Lett 248:89-95. 2007
    ..dominant disease with high penetrance, caused by germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6, PMS2 and MLH3...
  98. pmc Role of the mismatch repair gene, Msh6, in suppressing genome instability and radiation-induced mutations
    Julio Barrera-Oro
    Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
    Mutat Res 642:74-9. 2008
    ..Failure of this system can accelerate somatic mutation and increase the risk of developing cancer. MSH6, in complex with MSH2, is the MMR protein that mediates DNA repair through the recognition of 1- and 2-bp ..
  99. pmc Isolation and characterization of new proliferating cell nuclear antigen (POL30) mutator mutants that are defective in DNA mismatch repair
    Patrick J Lau
    Ludwig Institute for Cancer Research, Cancer Center, La Jolla, California 92093 0660, USA
    Mol Cell Biol 22:6669-80. 2002
    ..C81R) in the monomer-monomer interface region and resulted in a partial general MMR defect and a defect in MSH2-MSH6 binding in vitro...
  100. ncbi Correlation of mismatch repair genes immunohistochemistry and microsatellite instability status in HNPCC-associated tumours
    Andrew Ruszkiewicz
    Institute of Medical and Veterinary Science, Tissue Pathology, Royal Adelaide Hospital, Adelaide, South Australia
    Pathology 34:541-7. 2002
    The aim of this study was to assess the performance of immunohistochemistry using antibodies for MLH1, MSH2, MSH6 and PMS2 mismatch repair gene proteins against microsatellite instability (MSI) testing.
  101. pmc Clinical features and mismatch repair gene mutation screening in Chinese patients with hereditary nonpolyposis colorectal carcinoma
    Shan Run Liu
    Department of Surgery, Peking University First Hospital, Beijing 100034, China
    World J Gastroenterol 10:2647-51. 2004
    ..been associated with germline mutations in five mismatch repair (MMR) genes (hMSH2, hMLH1, hPMS1, hPMS2, and hMSH6/GTBP). The great majority of germline mutations were found in hMSH2 and hMLH1...

Research Grants53

  1. Repair of Oxidatively Damaged Guanines
    A LIEN L LU-CHANG; Fiscal Year: 2013
    ..To examine this hypothesis, we propose three specific aims: (1) The dynamic interaction of MYH with MSH2/MSH6 both in vitro and in vivo will be delineated...
  2. NEW HUMAN DNA REPAIR ENDONUCLEASE
    Alfonso Bellacosa; Fiscal Year: 2002
    ..Colorectal Cancer (HNPCC) carry a germline mutation in genes involved in DNA mismatch repair (h MSH2, h MLH1, GTBP /hMSH6, hPMS2 and hPMS1). These genes encode human homologues of the E. coli mismatch repair proteins MutS and MutL...
  3. Mismatch repair in V region mutation and isotype switching
    Matthew D Scharff; Fiscal Year: 2013
    ..We will do this by: 1) determining how MSH6 and the other mismatch repair proteins interact with PCNA to recruit error prone repair to the immunoglobulin ..
  4. Sapna Syngal; Fiscal Year: 2016
    ..by healthcare providers to estimate the probability that an individual carries a mutation in the MLH1, MSH2 and MSH6 mismatch repair (MMR) genes (Balmana et al. JAMA 2006, Kastrinos et. al Gastroenterology 2011)...
  5. Mechanistic studies of DNA repair and damage response
    Dorothy A Erie; Fiscal Year: 2010
    ..The MutS homolog MSH2-MSH6 (MutS) binds preferentially to a DNA lesion and subsequently interacts with the MutL homolog MLH1-PMS2 (MLH1-PMS1 ..
  6. PCNA clamp mechanisms in DNA replication and repair
    Manju M Hingorani; Fiscal Year: 2010
    ..With respect to a PCNA target, we plan to investigate the mechanism of action of S. cerevisiae Msh2-Msh6, an essential DNA mismatch repair protein that detects base pair errors in DNA and initiates repair in a an ATP-..
  7. Polly A Newcomb; Fiscal Year: 2014
    ..Participants have: (i) been tested for mutations in the mismatch repair genes (MLH1, MSH2, MSH6 and PMS2) and MUTYH, and measured for the single nucleotide polymorphisms (SNPs) known to be associated with CRC;(..
  8. Toward a molecular classification of human gliomas
    David N Louis; Fiscal Year: 2013
    ..agent used to treat all glioblastomas, temozolomide (TMZ), through a mechanism associated with inactivation of MSH6;MSH6-deficient glioblastomas grow more rapidly during TMZ therapy;and in vitro resources exist to evaluate defects ..
  9. Screening Pretest for HNPCC
    Jeremy Fields; Fiscal Year: 2007
    ..Aim 5. To study the feasibility of incorporating analyses for less frequent MMR mutations (MSH6)...
  10. SEAN VAHRAM TAVTIGIAN; Fiscal Year: 2016
    ..The most prominent high-risk colorectal cancer susceptibility genes, APC, MLH1, MSH2, MSH6, PMS2, and PTEN, were all discovered more than a decade ago...
  11. The Familial Colorectal Neoplasia Collaborative Group
    STEPHEN NORMAN THIBODEAU; Fiscal Year: 2011
    ..characterization core by continuing tumor phenotyping, performing germline mutation analysis on MLH1, MSH2, and MSH6 for the entire C-CFR, and dispatching products to other CFR sites for characterization of somatic MLH1 methylation ..
  12. INHERITED MSH6 MUTATIONS IN DIVERSE COLORECTAL CANCERS
    Sapna Syngal; Fiscal Year: 2004
    ..Recently, inherited mutations in a fifth mismatch repair gene, MSH6, have been identified in colorectal cancer patients...
  13. FAMILIAL COLORECTAL NEOPLASIA COLLABORATIVE GROUP
    Noralane Lindor; Fiscal Year: 2007
    ..characterization core by\par continuing tumor phenotyping, performing germline mutation analysis on MLH1, MSH2, and MSH6 for the\par entire C-CFR, and dispatching products to other CFR sites for characterization of somatic MLH1 ..
  14. Molecular Genetics of Colorectal Cancer Progression in a Diverse Patient Cohort
    BROOKE E SYLVESTER; Fiscal Year: 2011
    ..MLH1, MSH2, MSH6 and PMS2 are proteins expressed by mismatch repair genes that are responsible for repairing nucleotide mispairs and ..
  15. The Colon Cancer Family Registry: Hawaii
    Loic Le Marchand; Fiscal Year: 2011
    ..immunohistochemistry (IHC) for DNA mismatch repair (MMR) defect and testing for germ-line mutations in MLH1, MSH2, MSH6 and MYH for PHASE I samples. We have also enhanced the CFR data, especially with regard to diet and race/ethnicity...
  16. Function of the AID C terminus in Ig class switching
    JANET M STAVNEZER; Fiscal Year: 2013
    ..cooperatively with other enzymes involved in introducing DNA breaks into S regions, specifically UNG and Msh2-Msh6, and that this binding is dependent upon the AID C terminus...
  17. The Colon Cancer Family Registry: Seattle
    Polly A Newcomb; Fiscal Year: 2011
    ..Core activities by submitting participant biospecimen samples for: screening for expression of MLH1, MSH2, and MSH6 proteins;MMR-mutation testing guided by the IHC results;MLH1 methylation testing;screening for selected mutations ..
  18. Winfried Edelmann; Fiscal Year: 2016
    ..In new preliminary studies, we have modeled the pathogenic S144I HNPCC/LS mutation located in the MSH6-PWWP protein interaction domain, in knock-in mice...
  19. SEAN VAHRAM TAVTIGIAN; Fiscal Year: 2016
    ..cancer syndrome, is caused by germline mutations in one of four DNA mismatch repair (MMR) genes- MLH1, MSH2, MSH6, and PMS2...
  20. The Colon Cancer Family Registry: USC Consortium
    ROBERT WILLIAM HAILE; Fiscal Year: 2011
    ..families already in the Colon CFR who carry a deleterious mutation in a mismatch repair (MMR) gene (MLH1, MSH2, or MSH6), which will enable more informative analyses of penetrance and risk factors among carriers...
  21. Fay Kastrinos; Fiscal Year: 2014
    ..Lynch Syndrome: MMRpredict, MMRpro, and PREMM1,2,6 (prediction of mismatch repair gene mutations in MLH1, MSH2, and MSH6)...
  22. Anatoly Zhitkovich; Fiscal Year: 2016
    ..The induction of DSB required a sequential recruitment of MSH6- and MSH3-containing complexes, indicating the unprecedented cooperation of both MMR branches in processing of Cr-..
  23. Ajay Goel; Fiscal Year: 2016
    ..We will also look for evidence of methylation-induced silencing of the MSH2 and MSH6 genes, which also have CpG islands in their promoters, and should be susceptible to the same perturbation...
  24. Steven M Lipkin; Fiscal Year: 2014
    ..These complexes interact with MSH2/MSH6 and MSH2/MSH6 heterodimers...
  25. Multiscale modeling of supramolecular protein-DNA assemblies
    Michael Feig; Fiscal Year: 2013
    ..Applications focus on DNA mismatch recognition and initiation of repair by bacterial MutS and eukaryotic MSH2-MSH6 as well as transcription by yeast RNA polymerase II...
  26. DNA MISMATCH REPAIR IN EUKARYOTES
    Satya Prakash; Fiscal Year: 2003
    ..We will examine the roles of the Msh2-Msh3, Msh2-Msh6, and Mlh1-Pms1 complexes in mismatch recognition and in subsequent steps of mismatch repair and will determine at ..
  27. The Role of Mismatch Repair Factors in Class Switch Recombination
    ERIK LARSON; Fiscal Year: 2009
    ..clarifying the mechanism of class switch recombination by examining the role of the mismatch repair complex, MSH2/MSH6 (MutSalpha), in the pathway...
  28. PATHOPHYSIOLOGY OF PULMONARY SURFACTANT
    Sikandar Katyal; Fiscal Year: 1991
    ..Our recent results indicate that human SAP-A gene encodes both SAP-A and hydrophobic surfactant protein (HSAP). We have raised antisera to the hydrophobic proteins extracted from rat and human pulmonary surfactant...
  29. CRES GENE IN MALE REPRODUCTION
    Gail Cornwall; Fiscal Year: 1999
    ..These studies will provide valuable information on a novel epididymal protein which may be important for sperm development and maturation. ..
  30. DEFECTIVE DNA MISMATCH REPAIR IN ENDOMETRIAL CANCERS
    Paul Goodfellow; Fiscal Year: 2009
    ..We will also determine whether DMMR genes other than MSH2, MSH6 and MLH1 play significant roles in endometrial tumorigenesis...
  31. INTRACHROMOSOMAL RECOMBINATION IN MAMMALIAN CELLS
    ROBERT LISKAY; Fiscal Year: 2009
    Mutation in any one of five human DNA mismatch repair (MMR )gene homologs, MSH2, MSH6,MLH1, PMS2 and PMS1, contributes to both hereditary and spontaneous cancers...
  32. Discovery of Novel Genetic Variants Causing Colorectal *
    Steven Lipkin; Fiscal Year: 2005
    ..Because identifiable MLH1, MSH2 and MSH6 mutations in HNPCC underlie 2-5% of CRC patients, we hypothesize that more common susceptibility variants exist in ..
  33. Seattle Colorectal Cancer Family Registry (CFR)
    Polly Newcomb; Fiscal Year: 2007
    ..Core activities by submitting participant biospecimen\par samples for: screening for expression of MLH1, MSH2, and MSH6 proteins; MMR-mutation testing guided by\par the IHC results; MLH1 methylation testing; screening for selected ..
  34. DNA REPAIR IN EUKARYOTES
    GRAY CROUSE; Fiscal Year: 2002
    ..These studies focus on the yeast genes that are involved in nuclear mismatch repair: MSH2, MSH3 and MSH6. The products of these genes are responsible for the recognition of base distortions in the DNA and therefore begin ..
  35. PHENOTYPIC AND PSYCHOSOCIAL STUDY OF THE L1307K MUTATION
    Henry Lynch; Fiscal Year: 2004
    ....
  36. PREDISPOSING/MODIFYING GENES IN HEREDITARY COLON CANCER
    Paivi Peltomaki; Fiscal Year: 2001
    ..The aim is to identify genes that might modify the clinical phenotype of HNPCC, taking advantage of association and linkage-based approaches in these genetically homogeneous subsets of HNPCC patients. ..
  37. Hypomorphic Mismatch Repair Gene Mutations and Single Molecular MSI Analyses
    Steven Lipkin; Fiscal Year: 2007
    ..SPECIFIC AIM 2: To Test Single-Molecule MSI as a Validation Assay for Additional Predicted MLH1/MSH2 deleterious alleles in MSS CRCs. [unreadable] [unreadable] [unreadable]..
  38. MOLECULAR ANALYSES OF MLH3 NULL MICE
    Steven Lipkin; Fiscal Year: 2003
    ..mismatch repair genes associated with microsatellite instability have previously been described: MLH1, MSH2, MSH3, MSH6, PMS1, and PMS2...
  39. Molecular Profiling to Predict Response to Chemotherapy
    Johnathan Lancaster; Fiscal Year: 2006
    ..Ultimately, defining the biologic underpinnings of response to therapy will facilitate the development of more active agents that may improve cure rates for ovarian cancer. ..
  40. Ovarian Cancer and Mismatch Repair Deficiency
    Tuya Pal; Fiscal Year: 2009
    ..MSI may result from both genetic (i.e.: germline mutations in the MMR genes, including MLH1, MSH2, and MSH6) and epigenetic (i.e.: MLH1 promoter hypermethylation) mechanisms...
  41. P21 INDUCTION BY BRCA2
    Fergus Couch; Fiscal Year: 2002
    ....
  42. Molecul Biology of Intestinal Lipid Transport/Metabolism
    NICHOLAS DAVIDSON; Fiscal Year: 2003
    ..abstract_text> ..
  43. ANTI MUTAGENIC MISMATCH REPAIR OF UV DAMAGED DNA
    John Hays; Fiscal Year: 2004
    ..The abilities of MMR proteins to complete with NER proteins for mismatched- photoproduct substrates, thus preventing mutation-fixation by the latter, will also be tested. ..
  44. Insulin, the IGF Axis, and Colorectal Neoplasia
    Paul Limburg; Fiscal Year: 2005
    ..Following achievement of these goals, I am confident that I will be ready to continue my career as a successful independent investigator committed to academic research. ..
  45. Links between Mismatch Repair and Replication
    Hernan Flores Rozas; Fiscal Year: 2005
    ..cerevisiae and humans encode three MMR genes that are homologous to the E. coli MutS protein, MSH2, MSH3 and MSH6. Three yeast homologs of E. coli MutL are required for MMR, MLH1, PMS1 (PMS2 in humans) and MLH3...
  46. Repair of Oxidatively Damaged Guanines
    A Lien Lu Chang; Fiscal Year: 2008
    ..hypothesis, we propose the following specific aims: (1) The dynamic interactions of MYH with OGG1, NEIL1, and MSH2/MSH6 both in vitro and in vivo will be delineated...
  47. MECHANISTIC STUDIES OF DNA MISMATCH REPAIR
    A Lien Lu Chang; Fiscal Year: 2006
    ..Particularly, alterations in protein-protein interactions under oxidative stress will be investigated. These studies should advance our understanding of the role of DNA repair in genome stability and tumor susceptibility. ..
  48. Characterization of the Chromosome 17q23 Amplicon
    Fergus Couch; Fiscal Year: 2006
    ..Thus, the project may involve a complete transition from benchtop to bedside. Finally, the amplified and overexpressed genes may prove useful as important targets of gene, pharmacological, and immunological therapy in the future. ..
  49. Plasma Microarray Analysis and Ovarian Cancer Biomarkers
    Johnathan Lancaster; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  50. DNA Damage, Mutation and Cancer Gordon Conference
    John Hays; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  51. Gene expression profiles to predict ovarian cancer chemo-response in the elderly
    Johnathan Lancaster; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  52. DNA Damage, Mutation & Cancer Gordon Research Conference
    John Hays; Fiscal Year: 2008
    ..high-fidelity responses blocked replication forts. One will describe successive steps in pathways initiated by specific DNA lesions. [unreadable] [unreadable] [unreadable] [unreadable]..
  53. Molecular Epidemiology of Colorectal Cancer Subtypes
    Paul J Limburg; Fiscal Year: 2010
    ....