CHK2

Summary

Gene Symbol: CHK2
Description: checkpoint kinase 2
Alias: CDS1, CHK2, HuCds1, LFS2, PP1425, RAD53, hCds1, CHK2 checkpoint homolog, cds1 homolog, checkpoint-like protein CHK2, serine/threonine-protein kinase Chk2
Species: human

Top Publications

  1. ncbi CHK2 kinase: cancer susceptibility and cancer therapy - two sides of the same coin?
    Laurent Antoni
    Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Haddow Laboratories, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
    Nat Rev Cancer 7:925-36. 2007
  2. ncbi Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations
    Hanne Meijers-Heijboer
    Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
    Nat Genet 31:55-9. 2002
  3. pmc Family history, genetic testing, and clinical risk prediction: pooled analysis of CHEK2 1100delC in 1,828 bilateral breast cancers and 7,030 controls
    Olivia Fletcher
    Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London United Kingdom
    Cancer Epidemiol Biomarkers Prev 18:230-4. 2009
  4. ncbi The cell cycle checkpoint kinase Chk2 is a negative regulator of mitotic catastrophe
    Maria Castedo
    CNRS UMR 8125, Institut Gustave Roussy, 39 rue Camille Desmoulins, F 94805 Villejuif, France
    Oncogene 23:4353-61. 2004
  5. ncbi The EBNA-3 gene family proteins disrupt the G2/M checkpoint
    Kenia G Krauer
    Queensland Institute of Medical Research and Joint Oncology Program, University of Queensland, Brisbane, Australia
    Oncogene 23:1342-53. 2004
  6. doi The cell cycle checkpoint kinase CHK2 mediates DNA damage-induced stabilization of TTK/hMps1
    Y H Yeh
    Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
    Oncogene 28:1366-78. 2009
  7. doi The CHK2-BRCA1 tumour suppressor pathway ensures chromosomal stability in human somatic cells
    Ailine Stolz
    Philipps University Marburg, Institute for Molecular Biology and Tumour Research IMT, D 35037 Marburg, Germany
    Nat Cell Biol 12:492-9. 2010
  8. ncbi PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2
    Shutong Yang
    Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Nat Cell Biol 4:865-70. 2002
  9. ncbi DNA damage-induced activation of p53 by the checkpoint kinase Chk2
    A Hirao
    The Amgen Institute, Ontario Cancer Institute, and Departments of Medical Biophysics and Immunology, University of Toronto, 620 University Avenue, Suite 706, Toronto, Ontario, M5G 2C1, Canada
    Science 287:1824-7. 2000
  10. ncbi Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216
    C Y Peng
    Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Science 277:1501-5. 1997

Detail Information

Publications229 found, 100 shown here

  1. ncbi CHK2 kinase: cancer susceptibility and cancer therapy - two sides of the same coin?
    Laurent Antoni
    Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Haddow Laboratories, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
    Nat Rev Cancer 7:925-36. 2007
    In the past decade, CHK2 has emerged as an important multifunctional player in the DNA-damage response signalling pathway...
  2. ncbi Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations
    Hanne Meijers-Heijboer
    Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
    Nat Genet 31:55-9. 2002
    ..To find additional genes conferring susceptibility to breast cancer, we analyzed CHEK2 (also known as CHK2), which encodes a cell-cycle checkpoint kinase that is implicated in DNA repair processes involving BRCA1 and p53 (..
  3. pmc Family history, genetic testing, and clinical risk prediction: pooled analysis of CHEK2 1100delC in 1,828 bilateral breast cancers and 7,030 controls
    Olivia Fletcher
    Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London United Kingdom
    Cancer Epidemiol Biomarkers Prev 18:230-4. 2009
    ..Before such predictions are accepted by clinical geneticists, however, further population-based evidence is needed on the effect of CHEK2 1100delC and other moderate penetrance alleles in women with a family history of breast cancer...
  4. ncbi The cell cycle checkpoint kinase Chk2 is a negative regulator of mitotic catastrophe
    Maria Castedo
    CNRS UMR 8125, Institut Gustave Roussy, 39 rue Camille Desmoulins, F 94805 Villejuif, France
    Oncogene 23:4353-61. 2004
    ..that the down regulation of Cdk1/cyclin B is secondary to the activation of the DNA structure checkpoint kinase Chk2. Thus, syncytia generated by the fusion of asynchronous HeLa cells contain elevated levels of active Chk2 but not ..
  5. ncbi The EBNA-3 gene family proteins disrupt the G2/M checkpoint
    Kenia G Krauer
    Queensland Institute of Medical Research and Joint Oncology Program, University of Queensland, Brisbane, Australia
    Oncogene 23:1342-53. 2004
    ..The function of EBNA-3, -4 and -6 proteins appears to be more complex than anticipated and these data suggest a role for these proteins in disrupting the host cell cycle machinery...
  6. doi The cell cycle checkpoint kinase CHK2 mediates DNA damage-induced stabilization of TTK/hMps1
    Y H Yeh
    Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
    Oncogene 28:1366-78. 2009
    ..We have demonstrated previously that, upon DNA damage, TTK/hMps1 activates the checkpoint kinase CHK2 by phosphorylating CHK2 at Thr68...
  7. doi The CHK2-BRCA1 tumour suppressor pathway ensures chromosomal stability in human somatic cells
    Ailine Stolz
    Philipps University Marburg, Institute for Molecular Biology and Tumour Research IMT, D 35037 Marburg, Germany
    Nat Cell Biol 12:492-9. 2010
    ..The Chk2 kinase and its downstream targets p53 and Brca1 are tumour suppressors that have been functionally linked to the ..
  8. ncbi PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2
    Shutong Yang
    Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Nat Cell Biol 4:865-70. 2002
    ..The DNA damage checkpoint kinase hCds1/Chk2 is necessary for p53-dependent apoptosis after gamma irradiation...
  9. ncbi DNA damage-induced activation of p53 by the checkpoint kinase Chk2
    A Hirao
    The Amgen Institute, Ontario Cancer Institute, and Departments of Medical Biophysics and Immunology, University of Toronto, 620 University Avenue, Suite 706, Toronto, Ontario, M5G 2C1, Canada
    Science 287:1824-7. 2000
    b>Chk2 is a protein kinase that is activated in response to DNA damage and may regulate cell cycle arrest. We generated Chk2-deficient mouse cells by gene targeting...
  10. ncbi Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216
    C Y Peng
    Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Science 277:1501-5. 1997
    ..These results indicate that serine-216 phosphorylation and 14-3-3 binding negatively regulate Cdc25C and identify Cdc25C as a potential target of checkpoint control in human cells...
  11. ncbi Linkage of ATM to cell cycle regulation by the Chk2 protein kinase
    S Matsuoka
    Howard Hughes Medical Institute, Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Science 282:1893-7. 1998
    ..We identified Chk2, the mammalian homolog of the Saccharomyces cerevisiae Rad53 and Schizosaccharomyces pombe Cds1 protein kinases required for the DNA damage and replication checkpoints...
  12. pmc Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro
    S Matsuoka
    Howard Hughes Medical Institute, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 97:10389-94. 2000
    The protein kinase Chk2, the mammalian homolog of the budding yeast Rad53 and fission yeast Cds1 checkpoint kinases, is phosphorylated and activated in response to DNA damage by ionizing radiation (IR), UV irradiation, and replication ..
  13. ncbi Phosphorylation of threonine 68 promotes oligomerization and autophosphorylation of the Chk2 protein kinase via the forkhead-associated domain
    Joon Young Ahn
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Biol Chem 277:19389-95. 2002
    Phosphorylation of Thr-68 by the ataxia telangiectasia-mutated is necessary for efficient activation of Chk2 when cells are exposed to ionizing radiation...
  14. doi Evaluation of variants in the CHEK2, BRIP1 and PALB2 genes in an Irish breast cancer cohort
    N M McInerney
    Department of Surgery, Clinical Science Institute, University College Hospital, Galway, Ireland
    Breast Cancer Res Treat 121:203-10. 2010
    ..We found no evidence to suggest that PALB2 mutation is an important breast cancer predisposition gene in this population...
  15. ncbi CHEK2-positive breast cancers in young Polish women
    Cezary Cybulski
    International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
    Clin Cancer Res 12:4832-5. 2006
    ..To investigate the contribution of CHEK2 mutations to early-onset breast cancer in Poland and to establish the characteristic features of these cancers...
  16. doi Structure and activation mechanism of the CHK2 DNA damage checkpoint kinase
    Zhenjian Cai
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Mol Cell 35:818-29. 2009
    The CHK2 protein kinase is an important transducer of DNA damage checkpoint signals, and its mutation contributes to hereditary and sporadic cancer...
  17. pmc Chk2 mediates stabilization of the FoxM1 transcription factor to stimulate expression of DNA repair genes
    Yongjun Tan
    Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA
    Mol Cell Biol 27:1007-16. 2007
    ..Furthermore, FoxM1 protein is phosphorylated by checkpoint kinase 2 (Chk2) in response to DNA damage...
  18. pmc Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53
    N H Chehab
    Department of Molecular Genetics, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 14:278-88. 2000
    Chk2/hcds1, the human homolog of the Saccharomyces cerevisiae RAD53/SPK1 and Schizosaccharomyces pombe cds1 DNA damage checkpoint genes, encodes a protein kinase that is post-translationally modified after DNA damage...
  19. ncbi The association of sequence variants in DNA repair and cell cycle genes with cancers of the upper aerodigestive tract
    Janet Hall
    International Agency for Research on Cancer, Lyon, France
    Carcinogenesis 28:665-71. 2007
    ..While some of these associations are consistent with previous studies, we cannot rule out the possibility of false-positive associations. The positive findings should be explored in another large-scale study on UADT cancers...
  20. doi Chk2 oligomerization studied by phosphopeptide ligation: implications for regulation and phosphodependent interactions
    Jiejin Li
    Division of Molecular Structure, MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom
    J Biol Chem 283:36019-30. 2008
    Chk2/CHEK2/hCds1 is a modular serine-threonine kinase involved in transducing DNA damage signals. Phosphorylation by ataxia telangiectasia-mutated kinase (ATM) promotes Chk2 self-association, autophosphorylation, and activation...
  21. doi Short 42 degrees C heat shock induces phosphorylation and degradation of Cdc25A which depends on p38MAPK, Chk2 and 14.3.3
    Sibylle Madlener
    Institute of Clinical Pathology, Medical University of Vienna, Austria
    Hum Mol Genet 18:1990-2000. 2009
    ..Cdc25A degradation depended on Ser75-Cdc25A phosphorylation caused by p38MAPK and Chk2, which phosphorylated Ser177-Cdc25A that is specific for 14.3.3 binding...
  22. doi Estrogen receptor status in CHEK2-positive breast cancers: implications for chemoprevention
    C Cybulski
    Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
    Clin Genet 75:72-8. 2009
    ..01). Women with a CHEK2 mutation face a fourfold increase in the risk of ER-positive breast cancer and might be candidates for tamoxifen chemoprevention...
  23. pmc Mutation analysis of the CHK2 gene in breast carcinoma and other cancers
    Sigurdur Ingvarsson
    Institute for Experimental Pathology, University of Iceland, Reykjavik, Iceland
    Breast Cancer Res 4:R4. 2002
    Mutations in the CHK2 gene at chromosome 22q12.1 have been reported in families with Li-Fraumeni syndrome. Chk2 is an effector kinase that is activated in response to DNA damage and is involved in cell-cycle pathways and p53 pathways.
  24. ncbi The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis
    J Falck
    Institute of Cancer Bioloyg, Danish Cancer Society, Copenhagen, Denmark
    Nature 410:842-7. 2001
    ..Here we report a functional link between ATM, the checkpoint signalling kinase Chk2/Cds1 (Chk2) and Cdc25A, and implicate this mechanism in controlling the S-phase checkpoint...
  25. pmc Risk for contralateral breast cancer among carriers of the CHEK2*1100delC mutation in the WECARE Study
    L Mellemkjaer
    Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Br J Cancer 98:728-33. 2008
    ..However, the sampling variability was such that modest increases in risk could not be excluded. Nonetheless, because this is a rare mutation, it is unlikely to explain a major fraction of CBC in the population...
  26. doi The CHEK2 1100delC mutation is not present in Korean patients with breast cancer cases tested for BRCA1 and BRCA2 mutation
    Doo Ho Choi
    Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangnam Gu, Seoul, South Korea
    Breast Cancer Res Treat 112:569-73. 2008
    ..However, our results suggest that this mutation is absent or may be very infrequent in Korean patients with breast cancer who have high risk of BRCA1 and BRCA2 mutation, making its screening irrelevant from the practical point view...
  27. doi Effect of CHEK2 missense variant I157T on the risk of breast cancer in carriers of other CHEK2 or BRCA1 mutations
    C Cybulski
    International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, ul Połabska 4, Szczecin, Poland
    J Med Genet 46:132-5. 2009
    ..However, it is of interest to estimate the breast cancer risks associated with carrying two mutations because this information may be informative for genetic counsellors and may provide clues to the carcinogenic process...
  28. doi A novel Chk1/2-Lats2-14-3-3 signaling pathway regulates P-body formation in response to UV damage
    Nobuhiro Okada
    Department of Molecular Genetics, Research Institute for MicroFbial Diseases, Osaka University, 3 1 Yamadaoka, Suita City, Osaka 565 0871, Japan
    J Cell Sci 124:57-67. 2011
    ..UV) radiation, the Lats2 tumor suppressor protein is phosphorylated predominantly by Chk1 and weakly by Chk2 at S408 in vivo, and that this process occurs at all stages of the cell cycle and leads to phosphorylation of 14-3-..
  29. doi A simple method of investigating mutations in CHEK2 by DHPLC: a study of the German populations of Saxony, Saxony-Anhalt, and Thuringia
    Ulrike Scharrer
    Institute of Human Genetics, University of Leipzig, Germany
    Cancer Genet Cytogenet 199:48-52. 2010
    ..It can be easily integrated into diagnostic testing...
  30. ncbi Pathology of breast cancer in women with constitutional CHEK2 mutations
    Tomasz Huzarski
    Pomeranian Medical University, Szczecin, Poland
    Breast Cancer Res Treat 90:187-9. 2005
    ..6; p > 0.0001). This is the first report to demonstrate that different mutations of the same gene may be associated with specific histologic subtypes of cancer...
  31. ncbi Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2
    Jiejin Li
    Division of Protein Structure, National Institute for Medical Research, The Ridgeway, Mill Hill, London, United Kingdom
    Mol Cell 9:1045-54. 2002
    The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in cellular responses to DNA damage...
  32. ncbi Chk2 activates E2F-1 in response to DNA damage
    Craig Stevens
    Division of Biochemistry and Molecular Biology, Davidson Building, University of Glasgow, Glasgow, G12 8QQ, UK
    Nat Cell Biol 5:401-9. 2003
    ..We report that checkpoint kinase 2 (Chk2) regulates E2F-1 activity in response to the DNA-damaging agent etoposide...
  33. pmc Trans-activation of the DNA-damage signalling protein kinase Chk2 by T-loop exchange
    Antony W Oliver
    Section of Structural Biology, Cancer Research UK DNA Repair Enzymes Group, The Institute of Cancer Research, Chelsea, London, UK
    EMBO J 25:3179-90. 2006
    The protein kinase Chk2 (checkpoint kinase 2) is a major effector of the replication checkpoint. Chk2 activation is initiated by phosphorylation of Thr68, in the serine-glutamine/threonine-glutamine cluster domain (SCD), by ATM...
  34. pmc Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts
    Daphne W Bell
    Massachusetts General Hospital Cancer Center, Charlestown, MA, USA
    Int J Cancer 121:2661-7. 2007
    ....
  35. ncbi hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response
    J S Lee
    Laboratory of Molecular Hematology, NHLBI, NIH, Bethesda, Maryland 20892, USA
    Nature 404:201-4. 2000
    ..Here we report that the human Cds1 kinase (hCds1/Chk2) regulates BRCA1 function after DNA damage by phosphorylating serine 988 of BRCA1...
  36. doi Constitutional CHEK2 mutations are associated with a decreased risk of lung and laryngeal cancers
    Cezary Cybulski
    International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, ul Połabska 4, 70 115 Szczecin, Poland
    Carcinogenesis 29:762-5. 2008
    ..g. p53 mutations) and have a high level of genotoxic DNA damage induced by tobacco smoke. We speculate that lung cancer cells with impaired CHEK2 function undergo increased rates of cell death...
  37. ncbi Regulation of the Chk2 protein kinase by oligomerization-mediated cis- and trans-phosphorylation
    Julie K Schwarz
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Mol Cancer Res 1:598-609. 2003
    b>Chk2 is a serine/threonine protein kinase found mutated in certain hereditary and sporadic cancers. Ionizing radiation (IR) activates the kinase activity of Chk2 in a phosphorylation-dependent manner...
  38. ncbi The CHEK2 gene and inherited breast cancer susceptibility
    H Nevanlinna
    Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland
    Oncogene 25:5912-9. 2006
    Checkpoint kinase 2 (CHEK2, Chk2) emerges as an important signal transducer of cellular responses to DNA damage and a candidate tumor suppressor whose defects contribute to molecular pathogenesis of diverse types of human malignancies, ..
  39. pmc A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer
    Pia Vahteristo
    Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Haartmaninkatu 8, FIN 00029 HUS, Helsinki, Finland
    Am J Hum Genet 71:432-8. 2002
    CHEK2 (previously known as "CHK2") is a cell-cycle-checkpoint kinase that phosphorylates p53 and BRCA1 in response to DNA damage...
  40. ncbi HIV-1 Vpr induces ATM-dependent cellular signal with enhanced homologous recombination
    C Nakai-Murakami
    Department of Intractable Diseases, International Medical Center of Japan, Shinjuku ku, Tokyo, Japan
    Oncogene 26:477-86. 2007
    ..study, we present evidence that Vpr also activates ATM, and induces expression of gamma-H2AX and phosphorylation of Chk2. Strikingly, Vpr was found to stimulate the focus formation of Rad51 and BRCA1, which are involved in repair of DNA ..
  41. ncbi CHEK2 1100delC is not a risk factor for male breast cancer population
    Kirsi Syrjakoski
    Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland
    Int J Cancer 108:475-6. 2004
    ..A 1100delC mutation in CHEK2 (previously known as CHK2), a cell-cycle checkpoint kinase, has been implicated in predisposition of Li-Fraumeni syndrome (LFS) and breast ..
  42. ncbi A robust method for detecting CHK2/RAD53 mutations in genomic DNA
    Nayanta Sodha
    Royal Marsden NHS Trust, Surrey, UK
    Hum Mutat 19:173-7. 2002
    While screening for germline CHK2 mutations in cancer cases by heteroduplex CSGE, we observed that additional PCR fragments were generated from the 3' end region of the gene that includes exons 11-14...
  43. ncbi Breast cancer predisposing alleles in Poland
    B Gorski
    Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Polabska 4, Szczecin, Poland 70 115
    Breast Cancer Res Treat 92:19-24. 2005
    ..1) than for the missense mutation I157T (OR=1.4). This study suggests that cancer risks may be specific for particular alleles of a susceptibility gene and that these different risks should be taken into account by genetic counselors...
  44. ncbi Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population
    Avraham Shaag
    Department of Medicine Medical Genetics and Genome Sciences, University of Washington, Seattle, WA 98195 7720, USA
    Hum Mol Genet 14:555-63. 2005
    ..To assay these alleles for loss of CHEK2 function, we tested their capacity to complement Rad53 deletion in Saccharomyces cerevisiae. CHEK2...
  45. pmc The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype
    Hanne Meijers-Heijboer
    Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
    Am J Hum Genet 72:1308-14. 2003
    ..The unequivocal definition of the HBCC phenotype opens new avenues to search for this putative HBCC-susceptibility gene...
  46. ncbi Activated checkpoint kinase 2 provides a survival signal for tumor cells
    Jagadish C Ghosh
    Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Cancer Res 66:11576-9. 2006
    ..This is independent of p53, and requires activated checkpoint kinase 2 (Chk2), a putative tumor suppressor...
  47. ncbi Germline mutations in the CHEK2 kinase gene are associated with an increased risk of bladder cancer
    Elzbieta Złowocka
    International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
    Int J Cancer 122:583-6. 2008
    ..A CHEK2 mutation (all variants combined) was found in 10.6% of the cancer cases and in 5.9% of the controls (OR = 1.9; 95%CI 1.3-2.7; p = 0.0003). We conclude that CHEK2 mutations increase the risk of bladder cancer in the population...
  48. pmc Tumour characteristics and prognosis of breast cancer patients carrying the germline CHEK2*1100delC variant
    G H de Bock
    Department of Medical Decision Making, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
    J Med Genet 41:731-5. 2004
    ..The germline CHEK2*1100delC variant has been associated with breast cancer in multiple case families where involvement of BRCA1 and BRCA2 has been excluded...
  49. pmc DNA damage-induced cell cycle regulation and function of novel Chk2 phosphoresidues
    Giacomo Buscemi
    Department of Experimental Oncology, Istituto Nazionale Tumori, 20133 Milano, Italy
    Mol Cell Biol 26:7832-45. 2006
    b>Chk2 kinase is activated by DNA damage to regulate cell cycle arrest, DNA repair, and apoptosis...
  50. pmc Linkage disequilibrium mapping of CHEK2: common variation and breast cancer risk
    Kristjana Einarsdóttir
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
    PLoS Med 3:e168. 2006
    ..In this study, we aimed to assess the importance of common CHEK2 variants on population risk for breast cancer by capturing the majority of diversity in the gene using haplotype tagging single nucleotide polymorphisms (tagSNPs)...
  51. ncbi Caffeine abolishes the mammalian G(2)/M DNA damage checkpoint by inhibiting ataxia-telangiectasia-mutated kinase activity
    B B Zhou
    Department of Oncology Research, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 275:10342-8. 2000
    ..inhibits such a change and markedly reduces radiation-induced ataxia-telangiectasia-mutated (ATM)-dependent Chk2/Cds1 activation and phosphorylation...
  52. pmc Identification of women with an increased risk of developing radiation-induced breast cancer: a case only study
    Annegien Broeks
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Breast Cancer Res 9:R26. 2007
    ..Radiation exposure at a young age is one of the strongest risk factors for breast cancer. Germline mutations in genes involved in the DNA-damage repair pathway (DDRP) may render women more susceptible to radiation-induced breast cancer...
  53. ncbi CHK2-decreased protein expression and infrequent genetic alterations mainly occur in aggressive types of non-Hodgkin lymphomas
    Frederic Tort
    Laboratory of Pathology, Hospital Clinic, Institut d Investigacions Biomediques August Pi i Sunyer IDIBAPS, University of Barcelona, Spain
    Blood 100:4602-8. 2002
    The CHK2 gene codifies for a serine/threonine kinase that plays a central role in DNA damage response pathways...
  54. ncbi Uncommon CHEK2 mis-sense variant and reduced risk of tobacco-related cancers: case control study
    Paul Brennan
    International Agency for Research on Cancer IARC, Lyon, France
    Hum Mol Genet 16:1794-801. 2007
    ..g. by forcing nearby stem cells to divide before they have repaired their own DNA damage from tobacco smoke). If so, reducing the rate of apoptosis by reducing CHEK2 activity could be protective-although not smoking would be far more so...
  55. pmc CHEK2 I157T associates with familial and sporadic colorectal cancer
    O Kilpivaara
    J Med Genet 43:e34. 2006
    ..We investigated the CHEK2 I157T variant for colorectal cancer (CRC) predisposition in a large population based study including a significant number of familial CRC cases...
  56. ncbi MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways
    Zhenkun Lou
    Department of Oncology, Mayo Foundation, Rochester, Minnesota 55905, USA
    Nature 421:957-61. 2003
    ..MDC1 localizes to sites of DNA breaks and associates with CHK2 after DNA damage. This association is mediated by the MDC1 FHA domain and the phosphorylated Thr 68 of CHK2...
  57. ncbi Aberrations of the Chk2 tumour suppressor in advanced urinary bladder cancer
    Jirina Bartkova
    Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, Copenhagen DK 2100, Denmark
    Oncogene 23:8545-51. 2004
    Checkpoint kinase 2 (Chk2) is a tumour suppressor and signal transducer in genome integrity checkpoints that coordinate cell-cycle progression with DNA repair or cell death in response to DNA damage...
  58. pmc The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites
    S Y Shieh
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Genes Dev 14:289-300. 2000
    ..The human homolog of the second S. pombe checkpoint kinase, Cds1 (CHK2/hCds1), phosphorylates tetrameric p53 but not monomeric p53 in vitro at sites similar to those phosphorylated by hCHK1 ..
  59. ncbi Low frequency of the CHEK2*1100delC mutation among breast cancer probands from three regions of Poland
    E Kwiatkowska
    The Maria Sklodowska Curie Cancer Center and Institute of Oncology, 02781 Warsaw, Poland
    Neoplasma 53:305-8. 2006
    ..Further studies are still needed to evaluate the contribution of this mutation to the development of bilateral breast tumors...
  60. ncbi Colorectal cancer and the CHEK2 1100delC mutation
    Mirjam M de Jong
    Department of Gastroenterology, University of Groningen Medical Center, The Netherlands
    Genes Chromosomes Cancer 43:377-82. 2005
    ..Together, the results are consistent with a low-penetrance effect (OR 1.5-2.0) of the CHEK2 1100delC on CRC risk. Large case-control studies are required to clarify the exact role of the CHEK2 1100delC mutation in CRC...
  61. ncbi Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase
    H Fujimoto
    1Department of Genome Sciences, Faculty of Medical Sciences, Graduate School of Medicine, Kobe University, 7 5 1, Kusunoki cho, Chuo Ku, Kobe 650 0017, Japan
    Cell Death Differ 13:1170-80. 2006
    The antioncogenic Chk2 kinase plays a crucial role in DNA damage-induced cell-cycle checkpoint regulation...
  62. pmc Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility
    Mieke Schutte
    Department of Medical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands
    Am J Hum Genet 72:1023-8. 2003
    ..These results indicate that 1100delC may be the only CHEK2 allele that makes an appreciable contribution to breast cancer susceptibility...
  63. doi CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls
    Maren Weischer
    Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, Herlev, Denmark
    J Clin Oncol 26:542-8. 2008
    ..CHEK2*1100delC heterozygosity may be associated with an increased risk of breast cancer; however, it is unclear whether the evidence is sufficient to recommend genotyping in clinical practice...
  64. ncbi Breast cancer survival and tumor characteristics in premenopausal women carrying the CHEK2*1100delC germline mutation
    Marjanka K Schmidt
    Department of Epidemiology, Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
    J Clin Oncol 25:64-9. 2007
    ....
  65. ncbi Genetic and epigenetic analysis of CHEK2 in sporadic breast, colon, and ovarian cancers
    Louise H Williams
    Victorian Breast Cancer Research Consortium Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
    Clin Cancer Res 12:6967-72. 2006
    ..The aim of this study was to determine if somatic mutation and/or epigenetic modification play a role in development of sporadic breast, colon, or ovarian cancers...
  66. ncbi Human T-cell leukemia virus type 1 Tax oncoprotein prevents DNA damage-induced chromatin egress of hyperphosphorylated Chk2
    Saurabh K Gupta
    Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA
    J Biol Chem 282:29431-40. 2007
    ..We demonstrated previously that Tax associates with the cell cycle check point regulator Chk2 and proposed that the inappropriate activation of Chk2 provides a model for Tax-induced loss of genetic integrity (..
  67. ncbi Correlation of CHEK2 protein expression and c.1100delC mutation status with tumor characteristics among unselected breast cancer patients
    Outi Kilpivaara
    Department of Obstetrics and Gynecology, Helsinki University Central Hospital, FIN 00029 HUS, Finland
    Int J Cancer 113:575-80. 2005
    ..02). The c.1100delC germ line mutation also associated strongly with bilateral breast cancer. No significant correlation was seen between CHEK2 status and hormone receptor status, histology, lymph node status, or overall survival...
  68. pmc CHEK2 is a multiorgan cancer susceptibility gene
    C Cybulski
    International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
    Am J Hum Genet 75:1131-5. 2004
    ..0; P=.001), kidney cancer (OR 2.1; P=.0006), prostate cancer (OR 1.7; P=.002), and thyroid cancer (OR 1.9; P=.04). The range of cancers associated with mutations of the CHEK2 gene may be much greater than previously thought...
  69. ncbi German populations with infrequent CHEK2*1100delC and minor associations with early-onset and familial breast cancer
    Muhammad U Rashid
    Division of Molecular Genome Analysis, German Cancer Research Center, B055, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
    Eur J Cancer 41:2896-903. 2005
    ..In patients with a high-risk profile however, CHEK2*1100delC was indicative for this risk and highest for early-onset breast cancer...
  70. pmc HTLV-1 Tax oncoprotein subverts the cellular DNA damage response via binding to DNA-dependent protein kinase
    Sarah S Durkin
    Department of Microbiology and Molecular Cell Biology, Center for Biomedical Proteomics, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA
    J Biol Chem 283:36311-20. 2008
    ..Here we demonstrate that DNA-dependent protein kinase (DNA-PK) is a member of the Tax.Chk2 nuclear complex. The catalytic subunit, DNA-PKcs, and the regulatory subunit, Ku70, were present...
  71. ncbi Che-1 phosphorylation by ATM/ATR and Chk2 kinases activates p53 transcription and the G2/M checkpoint
    Tiziana Bruno
    Experimental Chemotherapy Laboratory, Department of Experimental Oncology, Regina Elena Cancer Institute, 00158 Rome, Italy
    Cancer Cell 10:473-86. 2006
    ..The checkpoint kinases ATM/ATR and Chk2 interact with Che-1 and promote its phosphorylation and accumulation in response to DNA damage...
  72. ncbi ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex
    Ji Hoon Lee
    Department of Molecular Genetics and Microbiology, Institute of Cellular and Molecular Biology, University of Texas at Austin, 1 University Station, A4800, Austin, TX 78712, USA
    Science 308:551-4. 2005
    ..in vitro with DNA in the presence of MRN, leading to phosphorylation of the downstream cellular targets p53 and Chk2. ATM autophosphorylation was not required for monomerization of ATM by MRN...
  73. ncbi Protein phosphatase 2A interacts with Chk2 and regulates phosphorylation at Thr-68 after cisplatin treatment of human ovarian cancer cells
    Xiaobing Liang
    Department of Biochemistry and Molecular Pharmacology, Mary Babb Randolph Cancer Center, Robert C Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506 9300, USA
    Int J Mol Med 17:703-8. 2006
    ..The checkpoint kinase, Chk2, has been implicated in both of these responses...
  74. ncbi CHEK2 variants predispose to benign, borderline and low-grade invasive ovarian tumors
    J Szymanska-Pasternak
    International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
    Gynecol Oncol 102:429-31. 2006
    ..Two founder alleles (1100delC and IVS2 + 1G >A) result in a truncated CHEK2 protein and the other is a missense substitution, leading to the replacement of a threonine with an isoleucine (I157T)...
  75. pmc CHEK2 1100delC in patients with metachronous cancers of the breast and the colorectum
    Anna Isinger
    Department of Oncology, Institute of Clinical Sciences, Lund University, 221 85 Lund, Sweden
    BMC Cancer 6:64. 2006
    ....
  76. ncbi Increased risk of breast cancer associated with CHEK2*1100delC
    Maren Weischer
    Department of Clinical Biochemistry, Herlev University Hospital, Herlev, Denmark
    J Clin Oncol 25:57-63. 2007
    ..We tested the hypothesis that CHEK2*1100delC heterozygosity in the general population increases the risk of cancer in general, and breast, prostate, and colorectal cancer in particular...
  77. ncbi Founder mutations in early-onset, familial and bilateral breast cancer patients from Russia
    Anna P Sokolenko
    N N Petrov Institute of Oncology, Pesochny 2, St Petersburg 197758, Russia
    Fam Cancer 6:281-6. 2007
    ..3%) patient each. No cases with BRCA1 300T>G (C61G) mutation was identified. The obtained data suggest that a significant fraction of hereditary BC cases in Russia can be diagnosed using only a limited number of simple PCR tests...
  78. ncbi CHEK2*1100delC is not an important high-risk gene in families with hereditary prostate cancer in southern Sweden
    M Wagenius
    Unit of Urology, Helsingborg Hospital, Helsingborg, Sweden
    Scand J Urol Nephrol 40:23-5. 2006
    ..CHEK2*1100delC is a frame-shifting germ-line mutation which abolishes the function of cell-cycle-checkpoint kinase 2 (chk2) and hence impairs the cells' response to DNA damage...
  79. ncbi Interaction between CHEK2*1100delC and other low-penetrance breast-cancer susceptibility genes: a familial study
    Nichola Johnson
    Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK
    Lancet 366:1554-7. 2005
    ..Our aim was to measure the risk of breast cancer in relatives of women with bilateral breast cancer who were carriers of this allele...
  80. ncbi The Wip1 phosphatase (PPM1D) antagonizes activation of the Chk2 tumour suppressor kinase
    M Oliva-Trastoy
    Service de Biochimie et de Génétique Moléculaire, CEA Saclay, Gif sur Yvette, France
    Oncogene 26:1449-58. 2007
    ..In response to DNA damage, ataxia telangiectasia mutated (ATM) phosphorylates the Chk2 tumour suppressor kinase at threonine 68 (Thr68), allowing Chk2 kinase dimerization and activation by ..
  81. ncbi Endogenous gamma-H2AX-ATM-Chk2 checkpoint activation in Bloom's syndrome helicase deficient cells is related to DNA replication arrested forks
    V Ashutosh Rao
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, U S Department of Health and Human Services, Bethesda, Maryland, USA
    Mol Cancer Res 5:713-24. 2007
    ..DNA double-strand break checkpoint response with prominent levels of phosphorylated histone H2AX (gamma-H2AX), Chk2 (p(T68)Chk2), and ATM (p(S1981)ATM) colocalizing in nuclear foci...
  82. ncbi Association of two mutations in the CHEK2 gene with breast cancer
    Natalia Bogdanova
    Gynecology Research Unit, Hannover Medical School, Hannover, Germany
    Int J Cancer 116:263-6. 2005
    ..Family history of breast cancer did not differ between carriers and noncarriers. Our data indicate that the I157T allele, and possibly the IVS2+1G > A allele, of the CHEK2 gene contribute to inherited breast cancer susceptibility...
  83. ncbi The CHEK2 c.1100delC germline mutation rarely contributes to breast cancer development in the Czech Republic
    Zdenek Kleibl
    Department of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, U nemocnice 5, Prague, 12853, Czech Republic
    Breast Cancer Res Treat 90:165-7. 2005
    ..1100delC mutation varies among different populations. Based on our results, genotyping of CHEK2 c.1100delC mutation in clinical settings in the Czech Republic could not be recommended...
  84. ncbi CHEK2 1100delC mutation is frequent among Russian breast cancer patients
    Elena V Chekmariova
    N N Petrov Institute of Oncology, St Petersburg, Russia
    Breast Cancer Res Treat 100:99-102. 2006
    ....
  85. ncbi A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase
    A Blasina
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Curr Biol 9:1-10. 1999
    ..The regulation of these enzymes is therefore likely to be crucial for the operation of the G2-M DNA-damage checkpoint...
  86. pmc Frequency of CHEK2*1100delC in New York breast cancer cases and controls
    Kenneth Offit
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    BMC Med Genet 4:1. 2003
    ..While the frequency of 1100delC was 1.1-1.4% in healthy Finnish controls, the frequency of this allele in a North American control population and in North American breast cancer kindreds remains unclear...
  87. ncbi Polo-like kinase 1 and Chk2 interact and co-localize to centrosomes and the midbody
    Lyuben Tsvetkov
    Department of Pathology, School of Medicine, Yale University, New Haven, Connecticut 06511, USA
    J Biol Chem 278:8468-75. 2003
    b>Chk2 is a protein kinase intermediary in DNA damage checkpoint pathways. DNA damage induces phosphorylation of Chk2 at multiple sites concomitant with activation...
  88. pmc CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours
    N Sodha
    Royal Marsden NHS Trust, Downs Road, Sutton, Surrey SM2 5PT, UK
    Br J Cancer 87:1445-8. 2002
    ....
  89. pmc Chk2 activation and phosphorylation-dependent oligomerization
    Xingzhi Xu
    Department of Pathology, School of Medicine, Yale University, New Haven, Connecticut 06510, USA
    Mol Cell Biol 22:4419-32. 2002
    The tumor suppressor gene CHK2 encodes a versatile effector serine/threonine kinase involved in responses to DNA damage...
  90. pmc Analysis of CHK2 in vulval neoplasia
    A Reddy
    Ludwig Institute for Cancer Research, Imperial College Faculty of Medicine, St Mary s Campus, Norfolk Place, London W2 1PG, UK
    Br J Cancer 86:756-60. 2002
    Structure and expression of the Rad53 homologue CHK2 were studied in vulval neoplasia...
  91. ncbi Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors
    Carl W Miller
    Division of Hematology Oncology, Department of Medicine, UCLA School of Medicine, Cedars Sinai Research Institute, 8700 Beverly Blvd, Davis 5019, Los Angeles, CA 90048, USA
    Genes Chromosomes Cancer 33:17-21. 2002
    ..Checkpoint kinase 2 (CHK2, CDS1, RAD53) is activated by ataxia telangiectasia mutated (ATM) in response to gamma irradiation...
  92. pmc Chk2 is required for HSV-1 ICP0-mediated G2/M arrest and enhancement of virus growth
    Han Li
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261, USA
    Virology 375:13-23. 2008
    ..Here we show that HSV-1-induced cell-cycle arrest at the G2/M border requires ICP0 and Chk2 kinase and that ICP0 expression by transfection or infection induces ATM-dependent phosphorylation of Chk2 and ..
  93. doi Frequency of the CHEK2 1100delC mutation among women with breast cancer: an international study
    Shiyu Zhang
    Women s College Research Institute, University Health Network, University of Toronto, Canada
    Cancer Res 68:2154-7. 2008
    ..We estimate that the CHEK2 1100delC allele is associated with an odds ratio of 2.6 for breast cancer, which corresponds to a lifetime risk of approximately 24% in Ontario...
  94. ncbi Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome
    S B Lee
    Massachusetts General Hospital Cancer Center and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA
    Cancer Res 61:8062-7. 2001
    ..with LFS without an inherited TP53 mutation, we have previously reported a truncating mutation (1100delC) in CHK2, encoding a kinase that phosphorylates p53 on Ser(20)...
  95. pmc Regulation of Chk2 ubiquitination and signaling through autophosphorylation of serine 379
    Christine M Lovly
    Department of Cell Biology and Physiology, Washington University School of Medicine, Box 8228, 660 S Euclid Ave, St Louis, MO 63110, USA
    Mol Cell Biol 28:5874-85. 2008
    The Chk2 protein kinase protects genome integrity by promoting cell cycle arrest or apoptosis in response to DNA double-strand breaks, and Chk2 mutations are found in both familial and sporadic cancers...
  96. ncbi The hCds1 (Chk2)-FHA domain is essential for a chain of phosphorylation events on hCds1 that is induced by ionizing radiation
    C H Lee
    Laboratory of Biochemical Genetics, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 1654, USA
    J Biol Chem 276:30537-41. 2001
    b>hCds1 (Chk2) is an evolutionarily conserved kinase that functions in DNA damage response and cell cycle checkpoint. The Cds1 family of kinases are activated by a family of large phosphatidylinositol 3-kinase-like kinases...
  97. ncbi ATR dependent activation of Chk2
    Xiao Qi Wang
    Department of Radiation Oncology, University of California Irvine, California, USA
    J Cell Physiol 208:613-9. 2006
    ..ATM and ATR are essential regulators of DNA damage checkpoints in mammalian cells through their respective effectors, Chk2 and Chk1...
  98. ncbi Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway
    P Chaturvedi
    Department of Oncology Research, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    Oncogene 18:4047-54. 1999
    ..We have cloned the rat and human homologs of Saccharomyces cerevisiae Rad 53 and Schizosaccharomyces pombe Cds1, called checkpoint kinase 2 (chk2)...
  99. pmc Activated checkpoint kinase 2 expression and risk for oral squamous cell carcinoma
    Angela J Yoon
    College of Dental Medicine, Division of Oral and Maxillofacial Pathology, Columbia University Medical Center, 630 West 168th Street, PH15W 1562, New York, NY 10032, USA
    Cancer Epidemiol Biomarkers Prev 16:2768-72. 2007
    ..Included in both groups were lesions with histologically confirmed dysplasia and those that lacked histologic evidence of atypia...
  100. ncbi Autophosphorylation of checkpoint kinase 2 at serine 516 is required for radiation-induced apoptosis
    Xianglin Wu
    Department of Oncology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    J Biol Chem 278:36163-8. 2003
    In response to ionizing radiation, checkpoint kinase 2 (Chk2) is activated in an ataxia telangiectasia mutation-dependent manner and induces either cell cycle arrest or apoptosis. Chk2 is also autophosphorylated following DNA damage...
  101. ncbi A novel founder CHEK2 mutation is associated with increased prostate cancer risk
    Cezary Cybulski
    International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
    Cancer Res 64:2677-9. 2004
    ..Our results provide evidence that the two truncating mutations of CHEK2 confer a moderate risk of prostate cancer in Polish men and that the missense change appears to confer a modest risk...

Research Grants64

  1. DNA Damage Checkpoint and Cancer
    Toru Ouchi; Fiscal Year: 2010
    ..pathways are responsible for arresting the cell cycle in response to damaged DNA - the ATR-Chk1 pathway and the ATM-Chk2 pathway...
  2. PROBES FOR CYTOMETRY
    Zbigniew Darzynkiewicz; Fiscal Year: 2010
    ..antibodies and multiparameter cytometry to measure phosphorylation/activation of key DDRs: histone H2AX, ATM, Chk2 and p53...
  3. Functional study of C53 protein as a novel regulator of checkpoint kinases
    Honglin Li; Fiscal Year: 2009
    ..activating a network of molecules including protein kinases ATM/ATR and their targets checkpoint kinases Chk1 and Chk2. By phosphorylating downstream effectors such as p53 and Cdc25 phosphatases, Chk1/Chk2 spread damage signal and ..
  4. Functional study of C53 protein as a novel regulator of checkpoint kinases
    Honglin Li; Fiscal Year: 2009
    ..activating a network of molecules including protein kinases ATM/ATR and their targets checkpoint kinases Chk1 and Chk2. By phosphorylating downstream effectors such as p53 and Cdc25 phosphatases, Chk1/Chk2 spread damage signal and ..
  5. Functional study of C53 protein as a novel regulator of checkpoint kinases
    Honglin Li; Fiscal Year: 2010
    ..activating a network of molecules including protein kinases ATM/ATR and their targets checkpoint kinases Chk1 and Chk2. By phosphorylating downstream effectors such as p53 and Cdc25 phosphatases, Chk1/Chk2 spread damage signal and ..
  6. Regulation of histone genes upon replication arrest and DNA damage
    HYERYUN PAIK; Fiscal Year: 2007
    ..We have discovered that the essential DNA damage checkpoint kinase Rad53 (the budding yeast homolog of the human tumor suppressor Chk2) is necessary for histone gene regulation following ..
  7. DNA DAMAGE RESPONSE AND DNA REPLICATION
    Jean Gautier; Fiscal Year: 2006
    ..We will determine whether the Xenopus homologues of Chk1 and/or Chk2/Cds1 are components of this pathway...
  8. New determinants of the DNA damage response in the fission yeast S. pombe
    MATTHEW J O apos CONNELL; Fiscal Year: 2010
    ..checkpoint is activated when the progression of DNA replication is impeded, and though its effector kinase Cds1, the stability of stalled replication forks is maintained to facilitate resumption of DNA replication...
  9. The role of DNA polymerase eta in DNA damage response and p53 activation
    Xinbin Chen; Fiscal Year: 2010
    ..Furthermore, we found that PolH modulates DNA damage response via the ATM- ChK2-p53 pathway...
  10. Analysis of Chk2 dependent DNA damage signaling pathway
    Junjie Chen; Fiscal Year: 2005
    ..b>Chk2, a DNA damage-activated protein kinase, regulates p53 and BRCA1 activities following gamma radiation...
  11. A Novel Pathway Involving ATM, PP1 and I-2
    Bo Xu; Fiscal Year: 2010
    ..Further, we found Brca1, Cdc7, and Chk2 presented in a complex with the phosphorylated form of I-2...
  12. A Novel Pathway Involving ATM, PP1 and I-2
    Bo Xu; Fiscal Year: 2010
    ..Further, we found Brca1, Cdc7, and Chk2 presented in a complex with the phosphorylated form of I-2...
  13. A Novel Pathway Involving ATM, PP1 and I-2
    Bo Xu; Fiscal Year: 2009
    ..Further, we found Brca1, Cdc7, and Chk2 presented in a complex with the phosphorylated form of I-2...
  14. DNA Damage Checkpoints
    Thanos Halazonetis; Fiscal Year: 2005
    ..the DNA damage checkpoint response (cell cycle arrest, apoptosis, radiosensitivity, activation of ATM, ATR, Chk1, Chk2, p53 and Cdc25C) in cells in which 53BP1 function is upregulated or downregulated...
  15. CELL CYCLE REGULATION OF THE YEAST HO GENE
    LINDA BREEDEN; Fiscal Year: 2001
    ..The Rad53 kinase has been previously shown to be required for the operation of the checkpoint...
  16. Biology of CHK2 Kinase In Lung Cancer
    Weixin Wang; Fiscal Year: 2005
    ..An immediate ATM downstream target, CHK2, plays a critical role in cell cycle checkpoint regulation and DNA damage induced apoptosis...
  17. ENZYMOLOGY OF REPLICATION OF YEAST CHROMOSOMAL DNA
    Peter M Burgers; Fiscal Year: 2010
    ..onto DNA with the sensor kinase Mec1 (human ATR), activates Mec1 to phosphorylate downstream targets including Rad53 (human Chk1/2)...
  18. ENZYMOLOGY OF REPLICATION OF YEAST CHROMOSOMAL DNA
    PETER BURGERS; Fiscal Year: 2009
    ..onto DNA with the sensor kinase Mec1 (human ATR), activates Mec1 to phosphorylate downstream targets including Rad53 (human Chk1/2)...
  19. Expression of Class I Specific Receptors in NK Cells
    David Raulet; Fiscal Year: 2009
    ..DNA lesions are recognized by sensor kinases ATM and/or ATR, which activate the checkpoint kinases, Chk2 and Chk1, p53, and ultimately lead to activation of the retinoblastoma protein pRb, cell cycle arrest, and ..
  20. Expression of Class I Specific Receptors in NK Cells
    David Raulet; Fiscal Year: 2007
    ..DNA lesions are recognized by sensor kinases ATM and/or ATR, which activate the checkpoint kinases, Chk2 and Chk1, p53, and ultimately lead to activation of the retinoblastoma protein pRb, cell cycle arrest, and ..
  21. Role of 53BP1 during the DNA damage response
    PHILLIP CARPENTER; Fiscal Year: 2006
    ..checkpoint genes including ATM (mutated in ataxia telangiectasia), BRCA1 (Breast cancer gene 1), p53, NBS1, and CHK2. Given the complexity of the cellular response to DNA damaging agents, there will undoubtedly be newly uncovered ..
  22. DNA Damage-Response Defects in Prostate Cancer Risk
    Wanguo Liu; Fiscal Year: 2009
    ..Indeed, we have demonstrated that germline mutations in CHK2 and p53AIP1 diminish their capacities to respond to DNA damage and increased prostate cancer risk, but more ..
  23. DNA Damage-Response Defects in Prostate Cancer Risk
    Wanguo Liu; Fiscal Year: 2010
    ..Indeed, we have demonstrated that germline mutations in CHK2 and p53AIP1 diminish their capacities to respond to DNA damage and increased prostate cancer risk, but more ..
  24. Regulatory networks in DNA damage checkpoint response
    Katsunori Sugimoto; Fiscal Year: 2010
    ..Phosphorylated Rad9 interacts with the Rad53 kinase, and the Rad9-Rad53 interaction increases Rad53 kinase activity...
  25. ATF2 in DNA damage response.
    ZE apos EV A RONAI; Fiscal Year: 2010
    ..Furthermore, ATF2 is also required for the activation of ATM, and consequently of Chk1 and Chk2. Significantly, the newly identified role of ATF2 in DNA damage response does not require its transcriptional ..
  26. ATF2 in DNA damage response.
    ZE EV RONAI; Fiscal Year: 2007
    ..Furthermore, ATF2 is also required for the activation of ATM, and consequently of Chk1 and Chk2. Significantly, the newly identified role of ATF2 in DNA damage response does not require its transcriptional ..
  27. ATF2 in DNA damage response.
    ZE EV RONAI; Fiscal Year: 2009
    ..Furthermore, ATF2 is also required for the activation of ATM, and consequently of Chk1 and Chk2. Significantly, the newly identified role of ATF2 in DNA damage response does not require its transcriptional ..
  28. DNA damage response and DDB
    Pradip Raychaudhuri; Fiscal Year: 2009
    ..of the PI3 kinases ATM/ATR with damaged chromatin and subsequent activation of the checkpoint kinases (Chk1 and Chk2) and p53, as well as other regulatory proteins that control the fate of a cell following DNA damage...
  29. Environmental exposure: Susceptibility alleles in a DNA damage response pathway
    Peter J Stambrook; Fiscal Year: 2010
    ..We will also ask whether such variants are over-represented in women who have had defined radiation exposure and now have developed breast cancer. ..
  30. GENETIC AND MOLECULAR ANALYSIS OF YEAST DNA REPLICATION
    Robert Sclafani; Fiscal Year: 2009
    ..of important cell cycle protein kinases, which include DDK (Cdc7-Dbf4), CDK (cyclin-dependent kinase) and the Rad53 checkpoint kinase. Three specific aims are proposed...