checkpoint kinase 2

Summary

Summary: Enzyme activated in response to DNA DAMAGE involved in cell cycle arrest. The gene is located on the long (q) arm of chromosome 22 at position 12.1. In humans it is encoded by the CHEK2 gene.

Top Publications

  1. Sheikh M, Malik Y, Zhu X. RA-Induced Transcriptional Silencing of Checkpoint Kinase-2 through Promoter Methylation by Dnmt3b Is Required for Neuronal Differentiation of P19 Cells. J Mol Biol. 2017;429:2463-2473 pubmed publisher
  2. Pilie P, Johnson A, Hanson K, Dayno M, Kapron A, Stoffel E, et al. Germline genetic variants in men with prostate cancer and one or more additional cancers. Cancer. 2017;123:3925-3932 pubmed publisher
    ..Likely pathogenic missense variants were identified in checkpoint kinase 2 (CHEK2) and homeobox protein Hox-B13 (HOXB13). In total, 11 of 102 patients (10...
  3. Chasovnikova O, Mitrofanov D, Anisimenko M, Voevoda M, Kovalenko S, Liakhovich V. [Prevalence of mutations BRCA1 5382insC, and CHEK2 1100delC in the population of Siberian region]. Genetika. 2012;48:768-72 pubmed
    ..25% for BRCA1 5382insC, and 1.78 versus 0.40% for CHEK2 1100delC) were observed, pointing to their association with susceptibility to breast cancer (OR = = 7.86, 95% CI 3.51-17.30 and OR =4.46, 95% C1 2.04-9.49, respectively). ..
  4. Symonds R, Jones G. Potential clinical exploitation of the radiation-induced DNA damage response. Clin Oncol (R Coll Radiol). 2014;26:241-2 pubmed publisher
  5. Hadjivassiliou H, Rosenberg O, Guthrie C. The crystal structure of S. cerevisiae Sad1, a catalytically inactive deubiquitinase that is broadly required for pre-mRNA splicing. RNA. 2014;20:656-69 pubmed publisher
  6. Damiola F, Pertesi M, Oliver J, Le Calvez Kelm F, Voegele C, Young E, et al. Rare key functional domain missense substitutions in MRE11A, RAD50, and NBN contribute to breast cancer susceptibility: results from a Breast Cancer Family Registry case-control mutation-screening study. Breast Cancer Res. 2014;16:R58 pubmed publisher
    ..However, the data neither establish whether variants in each of the three genes are best evaluated under the same analysis model nor achieve clinically actionable classification of individual variants observed in this study. ..
  7. Sánchez A, Gadaleta M, Limbo O, Russell P. Lingering single-strand breaks trigger Rad51-independent homology-directed repair of collapsed replication forks in the polynucleotide kinase/phosphatase mutant of fission yeast. PLoS Genet. 2017;13:e1007013 pubmed publisher
    ..From these data, we propose models for HDR-mediated tolerance of persistent SSBs with 3' phosphate in pnk1? cells. ..
  8. Couch F, Shimelis H, Hu C, Hart S, Polley E, Na J, et al. Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer. JAMA Oncol. 2017;3:1190-1196 pubmed publisher
  9. Galal S, Abdelsamie A, Shouman S, Attia Y, Ali H, Tabll A, et al. Part I: Design, synthesis and biological evaluation of novel pyrazole-benzimidazole conjugates as checkpoint kinase 2 (Chk2) inhibitors with studying their activities alone and in combination with genotoxic drugs. Eur J Med Chem. 2017;134:392-405 pubmed publisher
    Activated checkpoint kinase 2 (Chk2) is a tumor suppressor as one of the main enzymes that affect the cell cycle...

More Information

Publications27

  1. Einaga N, Yoshida A, Noda H, Suemitsu M, Nakayama Y, Sakurada A, et al. Assessment of the quality of DNA from various formalin-fixed paraffin-embedded (FFPE) tissues and the use of this DNA for next-generation sequencing (NGS) with no artifactual mutation. PLoS ONE. 2017;12:e0176280 pubmed publisher
    ..These results demonstrate that even FFPE tissues used for routine clinical diagnosis can be utilized to obtain reliable NGS data if appropriate conditions of fixation and validation are applied. ..
  2. Thibodeau M, Reisle C, Zhao E, Martin L, Alwelaie Y, Mungall K, et al. Genomic profiling of pelvic genital type leiomyosarcoma in a woman with a germline CHEK2:c.1100delC mutation and a concomitant diagnosis of metastatic invasive ductal breast carcinoma. Cold Spring Harb Mol Case Stud. 2017;3: pubmed publisher
    ..i>CHEK2 (checkpoint kinase 2) is a tumor-suppressor gene encoding a serine/threonine-protein kinase (CHEK2) involved in double-strand ..
  3. Zhou B, Elledge S. The DNA damage response: putting checkpoints in perspective. Nature. 2000;408:433-9 pubmed
    ..This pathway regulates known responses such as cell-cycle arrest and apoptosis (programmed cell death), and has recently been shown to control additional processes including direct activation of DNA repair networks. ..
  4. Chen E, Weng J, Chen Y, Wang S, Liu X, Huang W, et al. Phospho-Priming Confers Functionally Relevant Specificities for Rad53 Kinase Autophosphorylation. Biochemistry. 2017;56:5112-5124 pubmed publisher
    ..Our results show that, while Rad53 can display active conformations under various conditions, simulation of in vivo regulatory conditions confers functionally relevant autophosphorylation. ..
  5. Hollingworth R, Horniblow R, Forrest C, Stewart G, Grand R. Localization of Double-Strand Break Repair Proteins to Viral Replication Compartments following Lytic Reactivation of Kaposi's Sarcoma-Associated Herpesvirus. J Virol. 2017;91: pubmed publisher
    ..Overall, this study extends our understanding of the virus-host interactions that occur during lytic replication of KSHV and provides a deeper insight into how the DDR is manipulated during viral infection. ..
  6. Rinaldi V, Bolcun Filas E, Kogo H, Kurahashi H, Schimenti J. The DNA Damage Checkpoint Eliminates Mouse Oocytes with Chromosome Synapsis Failure. Mol Cell. 2017;67:1026-1036.e2 pubmed publisher
  7. Nikkilä J, Kumar R, Campbell J, Brandsma I, Pemberton H, Wallberg F, et al. Elevated APOBEC3B expression drives a kataegic-like mutation signature and replication stress-related therapeutic vulnerabilities in p53-defective cells. Br J Cancer. 2017;117:113-123 pubmed publisher
    ..Although loss of p53 might allow tumour cells to tolerate elevated APOBEC3B expression, continued expression of this enzyme might impart a number of therapeutic vulnerabilities upon tumour cells. ..
  8. Li Z, Liu J, Li J, Kong Y, Sandusky G, Rao X, et al. Polo-like kinase 1 (Plk1) overexpression enhances ionizing radiation-induced cancer formation in mice. J Biol Chem. 2017;292:17461-17472 pubmed publisher
    ..We conclude that Plk1 overexpression may contribute to tumor formation by both inducing chromosomal instability and suppressing the DDR pathway. ..
  9. Gan H, Yu C, Devbhandari S, Sharma S, Han J, Chabes A, et al. Checkpoint Kinase Rad53 Couples Leading- and Lagging-Strand DNA Synthesis under Replication Stress. Mol Cell. 2017;68:446-455.e3 pubmed publisher
    ..Therefore, we propose that Rad53 prevents the generation of excessive ssDNA under replication stress by coordinating DNA unwinding with synthesis of both strands. ..
  10. Takagi M, Yoshida M, Nemoto Y, Tamaichi H, Tsuchida R, Seki M, et al. Loss of DNA Damage Response in Neuroblastoma and Utility of a PARP Inhibitor. J Natl Cancer Inst. 2017;109: pubmed publisher
    ..Indeed, DDR-defective NB cell lines were sensitive to PARP inhibitors. Thus, PARP inhibitors represent candidate NB therapeutics. ..
  11. Chan K, Alonso Nuñez M, Grallert A, Tanaka K, Connolly Y, Smith D, et al. Dialogue between centrosomal entrance and exit scaffold pathways regulates mitotic commitment. J Cell Biol. 2017;216:2795-2812 pubmed publisher
    ..Such integration of signals emanating from neighboring scaffolds shows how centrosomes/SPBs can integrate inputs from multiple pathways to control cell fate. ..
  12. Boronat S, Domènech A, Carmona M, García Santamarina S, Bañó M, Ayte J, et al. Lack of a peroxiredoxin suppresses the lethality of cells devoid of electron donors by channelling electrons to oxidized ribonucleotide reductase. PLoS Genet. 2017;13:e1006858 pubmed publisher
  13. Pennisi R, Antoccia A, Leone S, Ascenzi P, di Masi A. Hsp90α regulates ATM and NBN functions in sensing and repair of DNA double-strand breaks. FEBS J. 2017;284:2378-2395 pubmed publisher
    ..Overall, present data shed light on the regulatory role of Hsp90α on the DDR, controlling ATM and NBN stability and influencing the DSBs signaling and repair. ..
  14. Ma X, Zhu X, Han Y, Story B, Do T, Song X, et al. Aubergine Controls Germline Stem Cell Self-Renewal and Progeny Differentiation via Distinct Mechanisms. Dev Cell. 2017;41:157-169.e5 pubmed publisher
  15. Crawford B, Adams S, Sittler T, van den Akker J, Chan S, Leitner O, et al. Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients. Breast Cancer Res Treat. 2017;163:383-390 pubmed publisher
    ..The identification of women with multiple pathogenic mutations has important implications for family testing. ..
  16. Balmana J, Diez O, Castiglione M. BRCA in breast cancer: ESMO clinical recommendations. Ann Oncol. 2009;20 Suppl 4:19-20 pubmed publisher
  17. Yeom S, Kim S, Jeong H, Jang K. Hepatitis B virus X protein activates E3 ubiquitin ligase Siah-1 to control virus propagation via a negative feedback loop. J Gen Virol. 2017;98:1774-1784 pubmed publisher
    ..For this effect, HBx sequentially activated ataxia telangiectasia mutated kinase and checkpoint kinase 2 via phosphorylation at the Ser-1981 and Thr-68 residues, respectively, which led to the activation of p53 ..
  18. Tung N, Silver D. Chek2 DNA damage response pathway and inherited breast cancer risk. J Clin Oncol. 2011;29:3813-5 pubmed publisher