CHK2

Summary

Gene Symbol: CHK2
Description: checkpoint kinase 2
Alias: CDS1, CHK2, HuCds1, LFS2, PP1425, RAD53, hCds1, serine/threonine-protein kinase Chk2, CHK2 checkpoint homolog, cds1 homolog, checkpoint-like protein 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 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
  3. 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
  4. 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
  5. pmc A mitotic phosphorylation feedback network connects Cdk1, Plk1, 53BP1, and Chk2 to inactivate the G(2)/M DNA damage checkpoint
    Marcel A T M van Vugt
    David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    PLoS Biol 8:e1000287. 2010
  6. doi A protein phosphatase feedback mechanism regulates the basal phosphorylation of Chk2 kinase in the absence of DNA damage
    Luigi Carlessi
    Dept of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy
    Biochim Biophys Acta 1803:1213-23. 2010
  7. 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
  8. 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
  9. 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
  10. 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

Research Grants

  1. GENETIC AND MOLECULAR ANALYSIS OF YEAST DNA REPLICATION
    Robert A Sclafani; Fiscal Year: 2012
  2. DNA Damage Checkpoint and Cancer
    Toru Ouchi; Fiscal Year: 2012
  3. Functional study of C53 protein as a novel regulator of checkpoint kinases
    Honglin Li; Fiscal Year: 2012
  4. Peter M Burgers; Fiscal Year: 2015
  5. Zbigniew Darzynkiewicz; Fiscal Year: 2014
  6. Michael B Yaffe; Fiscal Year: 2016
  7. A Novel Pathway Involving ATM, PP1 and I-2
    Sankar Mitra; Fiscal Year: 2012
  8. ATF2 in DNA damage response.
    ZE apos EV A RONAI; Fiscal Year: 2010
  9. TONY R HUNTER; Fiscal Year: 2016
  10. Regulatory networks in DNA damage checkpoint response
    KATSONURI SUGIMOTO; Fiscal Year: 2013

Detail Information

Publications274 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 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...
  3. 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 ..
  4. 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...
  5. pmc A mitotic phosphorylation feedback network connects Cdk1, Plk1, 53BP1, and Chk2 to inactivate the G(2)/M DNA damage checkpoint
    Marcel A T M van Vugt
    David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    PLoS Biol 8:e1000287. 2010
    ..Importantly, we show that Plk1 also phosphorylates the 53BP1-binding checkpoint kinase Chk2 to inactivate its FHA domain and inhibit its kinase activity in mammalian cells...
  6. doi A protein phosphatase feedback mechanism regulates the basal phosphorylation of Chk2 kinase in the absence of DNA damage
    Luigi Carlessi
    Dept of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy
    Biochim Biophys Acta 1803:1213-23. 2010
    The checkpoint kinase Chk2 is an effector component of the ATM-dependent DNA damage response (DDR) pathway. The activation of Chk2 by genotoxic stress involves its phosphorylation on T68 by ATM and additional auto/transphosphorylations...
  7. 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-..
  8. 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...
  9. 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 ..
  10. 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...
  11. ncbi Activation of ATM and Chk2 kinases in relation to the amount of DNA strand breaks
    Giacomo Buscemi
    Department of Experimental Oncology, Istituto Nazionale Tumori, Via G Venezian 1, 20133 Milan, Italy
    Oncogene 23:7691-700. 2004
    ..Here, we determined the kinetics of activation of the checkpoint kinases ATM and Chk2 (the latter substrate of ATM) in relation to the initial yield of genomic DNA single-strand (SSBs) and double-..
  12. 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...
  13. doi Per3, a circadian gene, is required for Chk2 activation in human cells
    Jun Sub Im
    Department of Biology Education, Seoul National University, Seoul, Republic of Korea
    FEBS Lett 584:4731-4. 2010
    ..Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells. In addition, Per3 physically interacted with ATM and Chk2...
  14. 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...
  15. pmc Naphthalimides induce G(2) arrest through the ATM-activated Chk2-executed pathway in HCT116 cells
    Hong Zhu
    Division of Anti tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China
    Neoplasia 11:1226-34. 2009
    ..Furthermore, depletion of Chk2, but not Chk1 with their corresponding siRNA, statistically significantly reversed the R16- and amonafide-triggered ..
  16. pmc Role of the ATM-checkpoint kinase 2 pathway in CDT-mediated apoptosis of gingival epithelial cells
    Mounia Alaoui-El-Azher
    Department of Oral Biology and Center for Molecular Microbiology, College of Dentistry, University of Florida, Gainesville, Florida, United States of America
    PLoS ONE 5:e11714. 2010
    ..inhibition and siRNA-silencing of the ATM downstream effector, the protein kinase checkpoint kinase 2 (Chk2), significantly impacted CDT-mediated apoptosis...
  17. pmc CHEK2 contribution to hereditary breast cancer in non-BRCA families
    Alexis Desrichard
    Laboratoire Diagnostic Génétique et Moléculaire, Centre Jean Perrin, 58 rue Montalembert, F 63011 Clermont Ferrand, France
    Breast Cancer Res 13:R119. 2011
    ..Previous studies have demonstrated an association between CHEK2 founder mutations and non-BRCA HBC. However, very few data on the entire coding sequence of this gene are available...
  18. pmc Roles of Kruppel-associated Box (KRAB)-associated Co-repressor KAP1 Ser-473 Phosphorylation in DNA Damage Response
    Chen Hu
    Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and College of Life Science and
    J Biol Chem 287:18937-52. 2012
    ..Ataxia telangiectasia mutated (ATM)-Chk2 and ATM- and Rad3-related (ATR)-Chk1 are two primary kinase signaling cascades activated in response to DNA damage...
  19. pmc Mammalian TIMELESS is required for ATM-dependent CHK2 activation and G2/M checkpoint control
    Xiaoming Yang
    Medical Chronobiology Laboratory, Wm Jennings Bryan Dorn Veterans Affairs Medical Center, Columbia, SC 29209, USA
    J Biol Chem 285:3030-4. 2010
    ..We report that TIM is likewise essential for ATM-dependent Chk2-mediated signaling of doxorubicin-induced DNA double strand breaks...
  20. 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 ..
  21. doi The checkpoint kinases Chk1 and Chk2 regulate the functional associations between hBRCA2 and Rad51 in response to DNA damage
    E M Bahassi
    Department of Cell and Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
    Oncogene 27:3977-85. 2008
    ..The checkpoint kinases Chk1 and Chk2 phosphorylate the carboxy-terminal domain of hBRCA2, a protein involved in recombination-mediated DNA repair (HRR) ..
  22. 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...
  23. 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...
  24. 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...
  25. 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...
  26. ncbi Priming phosphorylation of Chk2 by polo-like kinase 3 (Plk3) mediates its full activation by ATM and a downstream checkpoint in response to DNA damage
    El Mustapha Bahassi
    Department of Cell Biology, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267, USA
    Mutat Res 596:166-76. 2006
    The tumor suppressor gene Chk2 encodes a serine/threonine kinase that signals DNA damage to cell cycle checkpoints...
  27. ncbi Absence of CHEK2 1100delC mutation in familial breast cancer cases from a South American population
    Patricio Gonzalez-Hormazabal
    Breast Cancer Res Treat 110:543-5. 2008
  28. pmc Interdependent phosphorylation within the kinase domain T-loop Regulates CHK2 activity
    Xin Guo
    Department of Microbiology and Molecular Cell Biology, Cancer Biology and Infectious Disease Research Center, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA
    J Biol Chem 285:33348-57. 2010
    b>Chk2 is a critical regulator of the cellular DNA damage repair response. Activation of Chk2 in response to IR-induced damage is initiated by phosphorylation of the Chk2 SQ/TQ cluster domain at Ser(19), Ser(33), Ser(35), and Thr(68)...
  29. pmc Chk2 activation dependence on Nbs1 after DNA damage
    G Buscemi
    Department of Experimental Oncology, Istituto Nazionale Tumori, 20133 Milan, Italy
    Mol Cell Biol 21:5214-22. 2001
    The checkpoint kinase Chk2 has a key role in delaying cell cycle progression in response to DNA damage...
  30. ncbi Inducible degradation of checkpoint kinase 2 links to cisplatin-induced resistance in ovarian cancer cells
    Peilin Zhang
    Department of Pathology, West Virginia University, Morgantown, WV 26506, USA
    Biochem Biophys Res Commun 328:567-72. 2005
    Checkpoint kinase 2 (Chk2) is one of the critical kinases governing the cell cycle checkpoint, DNA damage repair, and cell apoptosis in response to DNA damaging signals...
  31. ncbi Stability of checkpoint kinase 2 is regulated via phosphorylation at serine 456
    Elizabeth M Kass
    Department of Biological Sciences, Columbia University, New York, New York, 10027 and Cell Signaling Technology, Inc, Danvers, Massachusetts 01923
    J Biol Chem 282:30311-21. 2007
    Checkpoint kinase 2 (Chk2), a DNA damage-activated protein kinase, is phosphorylated at Thr-68 by ataxia telangiectasia mutated leading to its activation by phosphorylation at several additional sites...
  32. ncbi Is CHEK2 a cause of the Li-Fraumeni syndrome?
    D G Evans
    J Med Genet 45:63-4. 2008
  33. pmc The DNA damage sensors ataxia-telangiectasia mutated kinase and checkpoint kinase 2 are required for hepatitis C virus RNA replication
    Yasuo Ariumi
    Department of Molecular Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2 5 1, Shikata cho, Okayama 700 8558, Japan
    J Virol 82:9639-46. 2008
    ..kinase (ATM), ATM- and Rad3-related kinase (ATR), poly(ADP-ribose) polymerase 1 (PARP-1), and checkpoint kinase 2 (Chk2), play central roles in the response to genotoxic stress, we hypothesized that these sensors might affect HCV ..
  34. pmc Taking the time to make important decisions: the checkpoint effector kinases Chk1 and Chk2 and the DNA damage response
    Travis H Stracker
    Molecular Biology, Sloan Kettering Institute, New York, NY, USA
    DNA Repair (Amst) 8:1047-54. 2009
    ..Key components of the DDR in mammalian cells are the checkpoint effector kinases Chk1 and Chk2 (referred to henceforth as the effector kinases; orthologous to spChk1 and spCds1 in the fission yeast S...
  35. pmc X-ray structures of checkpoint kinase 2 in complex with inhibitors that target its gatekeeper-dependent hydrophobic pocket
    George T Lountos
    Basic Science Program, SAIC Frederick, Frederick, MD 21702 1201, USA
    FEBS Lett 585:3245-9. 2011
    The serine/threonine checkpoint kinase 2 (Chk2) is an attractive molecular target for the development of small molecule inhibitors to treat cancer...
  36. doi CHEK2*1100delC homozygosity is associated with a high breast cancer risk in women
    Muriel A Adank
    Department of Clinical Genetics, VU University Medical Centre, Amsterdam, The Netherlands
    J Med Genet 48:860-3. 2011
    ..This study investigated the occurrence of homozygosity for the CHEK2*1100delC allele among familial breast cancer cases and the associated breast cancer risk...
  37. doi The effect of CHEK2 variant I157T on cancer susceptibility: evidence from a meta-analysis
    Fei fei Han
    Beijing Chao Yang Hospital, Capital Medical University, Beijing, China
    DNA Cell Biol 32:329-35. 2013
    ....
  38. pmc Phosphorylation at threonine 288 by cell cycle checkpoint kinase 2 (CHK2) controls human monopolar spindle 1 (Mps1) kinetochore localization
    Chun Wei Yeh
    From the Institute of Biomedical Sciences, Academia Sinica, 128 Sec 2, Academia Road, Taipei 115, Taiwan
    J Biol Chem 289:15319-27. 2014
    ..Here, we demonstrate that phosphorylation at Thr-288 by the cell cycle checkpoint kinase CHK2 is involved in this process...
  39. 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.
  40. 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...
  41. 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...
  42. 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...
  43. 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...
  44. 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...
  45. pmc The ATM/ATR signaling effector Chk2 is targeted by Epstein-Barr virus nuclear antigen 3C to release the G2/M cell cycle block
    Tathagata Choudhuri
    Department of Microbiology and the Tumor Virology Program, Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
    J Virol 81:6718-30. 2007
    ..Importantly, we show that the direct interaction of EBNA3C with Chk2, the ATM/ATR signaling effector, is responsible for the release of this nocodazole-induced G2/M arrest and that ..
  46. pmc Mutations in CHEK2 associated with prostate cancer risk
    Xiangyang Dong
    Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic Mayo Medical School, Rochester, MN 55905, USA
    Am J Hum Genet 72:270-80. 2003
    ..Overall, our data suggest that mutations in CHEK2 may contribute to prostate cancer risk and that the DNA-damage-signaling pathway may play an important role in the development of prostate cancer...
  47. ncbi Direct activation of the ATM protein kinase by 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 304:93-6. 2004
    ..We demonstrate that MRN stimulates the kinase activity of ATM in vitro toward its substrates p53, Chk2, and histone H2AX...
  48. 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 ..
  49. 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...
  50. 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...
  51. 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
    ....
  52. 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...
  53. 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...
  54. 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, ..
  55. pmc CHEK2 variants associate with hereditary prostate cancer
    E H Seppälä
    Laboratory of Cancer Genetics, Institute of Medical Technology, Lenkkeilijankatu 8, University of Tampere and Tampere University Hospital, FIN 33014 University of Tampere, Finland
    Br J Cancer 89:1966-70. 2003
    ..4% seen in the population controls. The results suggest that CHEK2 variants are low-penetrance prostate cancer predisposition alleles that contribute significantly to familial clustering of prostate cancer at the population level...
  56. 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...
  57. ncbi The Chk2 tumor suppressor is not required for p53 responses in human cancer cells
    Prasad V Jallepalli
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University, Baltimore, Maryland 21231, USA
    J Biol Chem 278:20475-9. 2003
    Ionizing radiation damages chromosomal DNA and activates p53-dependent transcription in mammalian cells. The Chk2 protein kinase has been hypothesized to be the primary mediator of this response...
  58. pmc Frequency of CHEK2 mutations in a population based, case-control study of breast cancer in young women
    Danielle M Friedrichsen
    Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
    Breast Cancer Res 6:R629-35. 2004
    ..However, the 1100delC mutation has only been investigated in a few population-based studies and none from North America...
  59. 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...
  60. 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...
  61. 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 ..
  62. 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...
  63. 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 ..
  64. 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...
  65. 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...
  66. 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)...
  67. 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...
  68. 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...
  69. 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...
  70. 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...
  71. 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...
  72. 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...
  73. 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...
  74. 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...
  75. 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...
  76. 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
    ..human homologs of Saccharomyces cerevisiae Rad 53 and Schizosaccharomyces pombe Cds1, called checkpoint kinase 2 (chk2)...
  77. 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...
  78. 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...
  79. 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...
  80. 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
    ....
  81. 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...
  82. 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...
  83. 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...
  84. ncbi Limited relevance of the CHEK2 gene in hereditary breast cancer
    Michael R Dufault
    Department of Medical Genetics, Munchen, Germany
    Int J Cancer 110:320-5. 2004
    ..Nevertheless, it seems premature to include CHEK2 screening in genetic testing...
  85. ncbi CHEK2 variant I157T may be associated with increased breast cancer risk
    Outi Kilpivaara
    Department of Obstetrics and Gynecology, Helsinki University Central Hospital HUCH, Helsinki, Finland
    Int J Cancer 111:543-7. 2004
    ..The I157T variant may be associated with breast cancer risk, but the risk is lower than for 1100delC...
  86. 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...
  87. 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...
  88. 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...
  89. 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
    ....
  90. 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...
  91. 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
    ....
  92. 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)...
  93. 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
    ....
  94. 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...
  95. 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...
  96. pmc CHEK2 1100delC is prevalent in Swedish early onset familial breast cancer
    Sara Margolin
    Department of Oncology, Karolinska University Hospital at Södersjukhuset, Stockholm, Sweden
    BMC Cancer 7:163. 2007
    ..A truncating variant, 1100delC, in check point-kinase CHEK2, has been identified as a risk factor for familial and sporadic breast cancer. The prevalence in healthy non-breast cancer cases is low and varies between populations...
  97. 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 ..
  98. 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...
  99. 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...
  100. 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...
  101. 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...

Research Grants63

  1. GENETIC AND MOLECULAR ANALYSIS OF YEAST DNA REPLICATION
    Robert A Sclafani; Fiscal Year: 2012
    ..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...
  2. DNA Damage Checkpoint and Cancer
    Toru Ouchi; Fiscal Year: 2012
    ..pathways are responsible for arresting the cell cycle in response to damaged DNA - the ATR-Chk1 pathway and the ATM-Chk2 pathway...
  3. Functional study of C53 protein as a novel regulator of checkpoint kinases
    Honglin Li; Fiscal Year: 2012
    ..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. Peter M Burgers; Fiscal Year: 2015
    ..onto DNA with the sensor kinase Mec1 (human ATR), activates Mec1 to phosphorylate downstream targets including Rad53 (human Chk1/2)...
  5. Zbigniew Darzynkiewicz; Fiscal Year: 2014
    ..antibodies and multiparameter cytometry to measure phosphorylation/activation of key DDRs: histone H2AX, ATM, Chk2 and p53...
  6. Michael B Yaffe; Fiscal Year: 2016
    ..to genotoxic stress, cells activate two canonical protein kinase pathways, the ATR-Chk1 pathway, and the ATM-Chk2 pathway...
  7. A Novel Pathway Involving ATM, PP1 and I-2
    Sankar Mitra; Fiscal Year: 2012
    ..Further, we found Brca1, Cdc7, and Chk2 presented in a complex with the phosphorylated form of I-2...
  8. 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 ..
  9. TONY R HUNTER; Fiscal Year: 2016
    ..The DNA damage response pathway involves activation of a series of protein kinases, including ATM, ATR, and Chk1/Chk2. To learn more about the network of events downstream of DNA damage, we will use SILAC labeling, phosphoprotein/..
  10. Regulatory networks in DNA damage checkpoint response
    KATSONURI SUGIMOTO; Fiscal Year: 2013
    ..Phosphorylated Rad9 interacts with the Rad53 kinase, and the Rad9-Rad53 interaction increases Rad53 kinase activity...
  11. RESTMD-CHARMM simulation of the Chk2/PP2A interaction in DNA repair
    SHANADEEN C BEGAY; Fiscal Year: 2011
    ..to simulate conformational changes caused by phosporylation during the interaction of cell cycle checkpoint kinase, CHK2), with Protein Phosphatase 2A (PP2A) to elucidate signaling mechanisms during the DMA damage response...
  12. Molecular Targeting of the Survivin Pathway in Cancer
    Dario C Altieri; Fiscal Year: 2010
    ..Emphasis will be placed on the role of the checkpoint kinase Chk2 in the regulation of mitochondrial survivin dynamics with respect to p53 requirements, recruitment of proapoptotic ..
  13. Susan L Forsburg; Fiscal Year: 2014
    ..Indeed, the S phase checkpoint kinase Cds1 (ScRad53) and the replication kinase Hsk1 and its subunit Dfp1 (ScCdc7, ScDbf4) which normally preserve replication ..
  14. John C Schimenti; Fiscal Year: 2016
    ..We identified checkpoint kinase 2 (CHK2;CHEK2) as an essential component of this response...
  15. Thomas M Aune; Fiscal Year: 2014
    ..To test this hypothesis, we will determine the extent to which this molecular and cellular phenotype is present in HLA-DRB1*04 positive and negative subjects with and without rheumatoid arthritis. ..
  16. Functional analysis of Chk2 in DNA damage response
    Jun Hyun Kim; Fiscal Year: 2013
    ..Extensive analyses of Chk2 and Rad53 (yeast Chk2 ortholog) have highlighted the important roles of Chk2 in S phase...
  17. Peter M Burgers; Fiscal Year: 2016
    ..A second protein kinase, Rad53, which is related to human Chk1 and Chk2, acts downstream in halting the cell cycle and activating other response ..
  18. Environmental exposure: Susceptibility alleles in a DNA damage response pathway
    Peter J Stambrook; Fiscal Year: 2013
    ..We will also ask whether such variants are over-represented in women who have had defined radiation exposure and now have developed breast cancer. ..
  19. The role of BRCA1 in nonhomologous repair of chromosomal double-strand breaks
    Fen Xia; Fiscal Year: 2010
    ..Through functional interaction with other DNA damage signaling and repair proteins including Chk2, Mre11 and Ku80, BRCA1 may orchestrate the repair of DSBs by competing mechanisms of homologous recombination (HR) ..
  20. Yuko Nakajima; Fiscal Year: 2014
    ..formation will be analyzed using molecular markers for SAC activity (Mad1 phosphorylation) and for DDC activity (Rad53 and Chk1 phosphorylation)...
  21. Radiation-Induced G1 Checkpoint Arrest in Yeast
    Stephen J Kron; Fiscal Year: 2010
    ..Our recent studies have linked activation of Rad9 and Rad53 to Rad9 assembly onto chromatin at sites of DNA damage, mediated by recognition of two specific chromatin marks, ..
  22. Chromatin structure and BRCA1 Checkpoint Function
    Roger A Greenberg; Fiscal Year: 2010
    ..BRCA1 is phosphorylated in response to DNA damage by the breast cancer suppressor checkpoint kinases ATM and CHK2, bolstering the concept that a BRCA1 dependent pathway of DNA repair is required to suppress malignancy...
  23. Activating liver carcinogens in yeast by expressing CYP450 polymorphisms
    MICHAEL THOMAS FASULLO; Fiscal Year: 2010
    ..induction of DNA repair genes after AFB1 exposure, and AFB1-associated activation of the checkpoint gene Rad53 (CHK2)...
  24. Resham Bhattacharya; Fiscal Year: 2016
    ..will be studied by changes in phosphorylation or localization of different markers including ATM1, ATR, Chk1 and Chk2. Cleavage of Caspase-3, 8, 9 and PARP will also be determined...
  25. Oleg Alekseev; Fiscal Year: 2015
    ..Furthermore, in neurons, which lack nuclear ATM and Chk2 and are incapable of mounting a DDR, HSV-1 infection is typically latent...
  26. Genetic Analysis of MSM Protein Function in S. Pombe
    Susan L Forsburg; Fiscal Year: 2012
    ..evidence that the MCM complex, and particularly Mcm4, is a substrate of the replication checkpoint kinase Cds1. It analyzes mutant forms of Mcm4 that disrupt checkpoint response for their effects on protein recruitment and ..
  27. New determinants of the DNA damage response in the fission yeast S. pombe
    MATTHEW J O'CONNELL; Fiscal Year: 2013
    ..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...
  28. Michael B Kastan; Fiscal Year: 2016
    ..Preliminary data now also implicate the ATM and Chk2 kinases and the HuR translational regulatory protein in this pathway...
  29. Liza A Pon; Fiscal Year: 2016
    ..We also find that Rad53p, the yeast homologue of the tumor suppressor and the DNA damage checkpoint kinase Chk2, regulates G1 to S progression in response to loss of mtDNA...
  30. Simon N Powell; Fiscal Year: 2016
    ..BRCA1 is activated to promote homologous recombination by a critical post-translational modification by Chk2 on serine 988, which then results in controlling the extent of 5'-end resection at double- strand breaks...
  31. Jiandong Chen; Fiscal Year: 2014
    ..DNA damage induces MDMX phosphorylation by ATM and Chk2, leading to its degradation by MDM2...
  32. The Role of Caspase Activation in the Differentiation-Dependent Life Cycle of HPV
    Cary A Moody; Fiscal Year: 2012
    ..which is necessary for efficient viral genome amplification, as well as caspase activation through the ATM target Chk2. Based on the finding that caspase activation, as well as Chk2 activation, can be stimulated by both E6 and E7, and ..
  33. Wendell G Yarbrough; Fiscal Year: 2016
    ..mediated, at least in part, by LZAP abrogation of the G2/M checkpoint through binding and inhibition of Chk1 and Chk2. Human tumor and xenograft mouse tumor data, as well as, LZAP activities as an activator of p53 and suppressor of ..
  34. EBNA3C and tumor supressors
    Erle S Robertson; Fiscal Year: 2010
    ..We will investigate the phosphorylation status of p53 by kinases which include CyclinA/Cdk2, Chk1, Chk2 and ATM which prevents Mdm2 targeted ubiquitination and test the ability of EBNA3C to modulate the function of Mdm2 ..
  35. Mitotic Response to DNA damage
    WILLIAM EDWARD THEURKAUF; Fiscal Year: 2010
    ..Further, this mitotic damage response required the Chk2 kinase tumor suppressor homologue, and Chk2 localizes to centrosomes, chromosomes, and the midbody...
  36. MICAH ALAN LUFTIG; Fiscal Year: 2016
    ..First, we will determine the critical effectors of the ATM/Chk2 dependent DDR detected early after EBV infection...
  37. 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 ..
  38. Jian Ting Zhang; Fiscal Year: 2014
    ..in cellular response to radiation-induced apoptosis;(2) to determine if increased stratifin expression regulates Chk2 which, in turn, regulates cell cycle checkpoint for DNA repair and survival;(3) to determine the mechanism of ..
  39. Xinbin Chen; Fiscal Year: 2014
    ..Furthermore, we found that PolH modulates DNA damage response via the ATM- ChK2-p53 pathway...
  40. 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 ..
  41. Laimonis A Laimins; Fiscal Year: 2016
    ..The ATM pathway appears to be linked to caspase activation as inhibitors of Chk2 block caspase cleavage...
  42. 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...
  43. 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 ..
  44. 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...
  45. JOSEPH VINCENT BONVENTRE; Fiscal Year: 2016
    ..temporal characteristics of ATM/ATR activation and their downstream effectors (including cyclin D1, ELF4/MEF, CHK1, CHK2, p53 and gH2AX) and relate these findings to the differentiation status of the PTC...
  46. Aurora-A/BTAK/STK15 Oncoprotein in Mitotic Spindle Assembly and Checkpoint Respon
    Subrata Sen; Fiscal Year: 2012
    ..4. Investigate the role of two novel Aurora-A interacting proteins, the Chk2 kinase and the mitochondrial membrane protein MTP18 in the survival of cells and in the activation of mitotic cell ..
  47. STEPHEN KNOX JONES; Fiscal Year: 2014
    ..I hypothesize that the thioredoxin pathway and Rad53 pathways are involved, so they will be tested using gene deletion and over-expression strains for TRX1, TRR1, CAP1,..
  48. MARK A PEIFER; Fiscal Year: 2015
    ..Aim we will determine how APC and its partners act to regulate centrosome migration and thus ensure high fidelity chromosome segregation, and explore how Chk2 and other checkpoint regulators buffer the errors that occur in its absence.
  49. Single Stranded DNA: The Genome's Achilles Heel
    Wenyi Feng; Fiscal Year: 2009
    ..base this hypothesis on the following observations: (1) Saccharomyces cerevisiae replication checkpoint-deficient rad53 mutant cells contain stalled replication forks and accumulate large regions of ssDNA upon treatment with the ..
  50. 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...
  51. Zahid H Siddik; Fiscal Year: 2015
    ..Based on the strong relationship of mutual exclusivity, tumors with wild-type p53 are likely to have defective Chk2 expression, and this defect will impact post-translational modification of p53 that is essential for stabilization ..
  52. John V Heymach; Fiscal Year: 2015
    ..We have also identified several targets, including telomerase and Chk2, for overcoming radioresistance...
  53. TOMAS D WALSH; Fiscal Year: 2015
    ..Discovery of new breast cancer susceptibility genes will allow prevention strategies to be extended to families for which causal genes are currently unknown. ..
  54. Deregulation of the Ubiquitin/26S Proteasome Pathway in AT cells: Role of ISG15
    SHYAMAL DESAI; Fiscal Year: 2009
    ..ATM is a 370 kDa nuclear Ser/Thr kinase contributing to the regulation of p53, BRCA1, and Chk2 signaling pathways, amongst others, and thus required for progression through mitotic checkpoints, double strand ..
  55. PHOSPHOLIPIDS--MEMBRANE SYNTHESIS & SIGNAL TRANSDUCTION
    William Dowhan; Fiscal Year: 2000
    ..will focus on a central step of phospholipid metabolism catalyzed by the CDP-diacylglycerol (-DAG) synthase (CDS1 gene product) which provides the precursor to the major phospholipids found in all organelles of eukaryotic cells ..
  56. Role of MRK in DNA Damage Response
    Rosamaria Ruggieri; Fiscal Year: 2007
    ..The ATM-Chk2/Chkl-Cdc25A cascade, downstream of the BRCT-motif-containing proteins MCD1, Nbsl and 53BP1, plays an important role ..
  57. CELLULAR PHARMACOLOGY IN CANCER CHEMOTHERAPY
    William Plunkett; Fiscal Year: 2006
    ..The role of inhibitory phosphorylations of Cdk2 in the regulatory hierarchy involving Cdc25A, Chkl and Chk2 will be defined, and we will evaluate the role of cyclin dependent kinase inhibitors such as p21 with respect to ..
  58. Chemoprevention Through Activation of Estrogen Receptor Alpha-Induced Senescence
    Harikrishna Nakshatri; Fiscal Year: 2007
    ..2) Senescence-like growth arrest was accompanied with activation of p53 and the checkpoint kinase Chk2 and induction of the senescence-associated gene Cst1...
  59. Extending Safe and Effective Thrombolysis for Stroke
    David Kent; Fiscal Year: 2005
    ..physicians), we propose to develop a set of tools incorporated into a computer-based decision-support instrument (CDS1) for use in real time...
  60. Nitrosourea-induced growth arrest and apoptotic pathways
    Kevin Brown; Fiscal Year: 2007
    ..to play a key role in MNNG-induced responses, is required for the ATM-dependent activation of the checkpoint kinase Chk2. We hypothesize that MNNG treatment activates multiple pathways that control cell cycle arrest and apoptosis...
  61. Role of E2F1 in eugenol-mediated antiproliferative activity in melanoma cells
    Rita Ghosh; Fiscal Year: 2009
    ..We have proposed that following eugenol treatment DNA damage signaling occurs through ATM/chk2 pathway that leads to stabilization of E2F1...
  62. The role of hBUB1-p53 pathway in genomic stability.
    Sam Thiagalingam; Fiscal Year: 2007
    ..Additionally, despite their lower frequency, mutations in Chk1 and Chk2, upstream modulators of p53, were found in a minority of tumors that lack intra-geneic p53 alterations which ..
  63. Mechanisms of the Human S-phase DNA Damage Checkpoint
    Jun Qin; Fiscal Year: 2006
    ..One pathway for the activation of S-phase checkpoint is ATM/CHK2/CDC25A, in which ATM/CHK2 regulates the degradation of the cell cycle regulator CDC25A through the poly-..