checkpoint kinase 1

Summary

Summary: A serine/threonine-specific protein kinase which is encoded by the CHEK1 gene in humans. Checkpoint kinase 1 (also known as Chk1) coordinates DNA damage response and cell cycle checkpoint response. Under these conditions, activation of Chk1 results in the initiation of cell cycle checkpoints, cell cycle arrest, DNA repair and cell death, to prevent damaged cells from progressing through the cell cycle.

Top Publications

  1. 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. ..
  2. Babiker H, McBride A, Cooke L, Mahadevan D. Therapeutic potential of investigational CHK-1 inhibitors for the treatment of solid tumors. Expert Opin Investig Drugs. 2017;26:1063-1072 pubmed publisher
    ..The safety of the aforementioned combination needs to be closely evaluated in the ongoing clinical trials. ..
  3. 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
  4. Colicchia V, Petroni M, Guarguaglini G, Sardina F, Sahún Roncero M, Carbonari M, et al. PARP inhibitors enhance replication stress and cause mitotic catastrophe in MYCN-dependent neuroblastoma. Oncogene. 2017;36:4682-4691 pubmed publisher
    ..These data highlight a novel route for cell death induction by PARP inhibitors and support their introduction, together with CHK1 inhibitors, in therapeutic approaches for neuroblastomas with high MYC(N) activity. ..
  5. 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. ..
  6. Oshikawa M, Okada K, Tabata H, Nagata K, Ajioka I. Dnmt1-dependent Chk1 pathway suppression is protective against neuron division. Development. 2017;144:3303-3314 pubmed publisher
    ..b>Checkpoint kinase 1 (Chk1) pathway activation during the S phase prevented the cell death, and allowed the division of cortical ..
  7. Green A, Budagyan K, Hayer K, Reed M, Savani M, Wertheim G, et al. Cytosine Deaminase APOBEC3A Sensitizes Leukemia Cells to Inhibition of the DNA Replication Checkpoint. Cancer Res. 2017;77:4579-4588 pubmed publisher
    ..i>Cancer Res; 77(17); 4579-88. ©2017 AACR. ..
  8. Matsuda S, Hammaker D, Topolewski K, Briegel K, Boyle D, DOWDY S, et al. Regulation of the Cell Cycle and Inflammatory Arthritis by the Transcription Cofactor LBH Gene. J Immunol. 2017;199:2316-2322 pubmed publisher
    ..Decreased DNA polymerase ? was followed by checkpoint arrest due to phosphorylation of checkpoint kinase 1. Because DNA fragments can increase arthritis severity in preclinical models, we then explored the effect ..
  9. Webster J, Tibes R, Morris L, Blackford A, Litzow M, Patnaik M, et al. Randomized phase II trial of cytosine arabinoside with and without the CHK1 inhibitor MK-8776 in relapsed and refractory acute myeloid leukemia. Leuk Res. 2017;61:108-116 pubmed publisher
    ..Incorporation of AraC into DNA activates checkpoint kinase 1 (Chk1), leading to cell-cycle arrest and diminished AraC cytotoxicity, which can be reversed by the ..

More Information

Publications21

  1. Chen H, Wang L, Wang W, Cheng C, Zhang Y, Zhou Y, et al. ELABELA and an ELABELA Fragment Protect against AKI. J Am Soc Nephrol. 2017;28:2694-2707 pubmed publisher
    ..Together, our results suggest that ELA32 and ELA11 may be therapeutic candidates for treating AKI. ..
  2. 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. ..
  3. Liu Y, Li Y, Wang X, Liu F, Gao P, Quinn M, et al. Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of Lkb1-Deficient Lung Adenocarcinoma. Cancer Res. 2017;77:5068-5076 pubmed publisher
    ..i>Cancer Res; 77(18); 5068-76. ©2017 AACR. ..
  4. 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. ..
  5. 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. ..
  6. Paculova H, Kramara J, Simečková S, Fedr R, Soucek K, Hylse O, et al. BRCA1 or CDK12 loss sensitizes cells to CHK1 inhibitors. Tumour Biol. 2017;39:1010428317727479 pubmed publisher
    ..Therefore, we suggest CHK1 inhibition as a strategy for targeting BRCA1- or CDK12-deficient tumors...
  7. Iwata T, Uchino T, Koyama A, Johmura Y, Koyama K, Saito T, et al. The G2 checkpoint inhibitor CBP-93872 increases the sensitivity of colorectal and pancreatic cancer cells to chemotherapy. PLoS ONE. 2017;12:e0178221 pubmed publisher
    ..Our results thus reveal that combination treatment of CBP-93872 with known chemotherapeutic agents inhibits phosphorylation of ATR and Chk1, and induces cell death. ..
  8. Sen T, Tong P, Stewart C, Cristea S, Valliani A, Shames D, et al. CHK1 Inhibition in Small-Cell Lung Cancer Produces Single-Agent Activity in Biomarker-Defined Disease Subsets and Combination Activity with Cisplatin or Olaparib. Cancer Res. 2017;77:3870-3884 pubmed publisher
    ..Our findings provide a preclinical proof of concept supporting the initiation of a clinical efficacy trial in patients with platinum-sensitive or platinum-resistant relapsed SCLC. Cancer Res; 77(14); 3870-84. ©2017 AACR. ..
  9. Barba M, Vici P, Pizzuti L, Di Lauro L, Sergi D, Di Benedetto A, et al. Body mass index modifies the relationship between γ-H2AX, a DNA damage biomarker, and pathological complete response in triple-negative breast cancer. BMC Cancer. 2017;17:101 pubmed publisher
    ..between DDR biomarkers, namely phosphorylated H2A Histone Family Member X (γ-H2AX) and phosphorylated checkpoint kinase 1 (pChk1), and pCR was reconsidered in light of BMI data...
  10. Willis J, Destephanis D, Patel Y, Gowda V, Yan S. Study of the DNA damage checkpoint using Xenopus egg extracts. J Vis Exp. 2012;:e4449 pubmed publisher
    ..Activated ATR can phosphorylate its downstream substrates such as Chk1 (Checkpoint kinase 1)...
  11. Holden J, Taylor E, Lindsay H. Cip29 is phosphorylated following activation of the DNA damage response in Xenopus egg extracts. PLoS ONE. 2017;12:e0181131 pubmed publisher
    ..Taken together, these data identify Cip29 as a novel target of the DNA damage response and suggest that the damage-dependent modification of Cip29 may relate to a role in the regulation of gene expression after DNA damage. ..
  12. Collart C, Smith J, Zegerman P. Chk1 Inhibition of the Replication Factor Drf1 Guarantees Cell-Cycle Elongation at the Xenopus laevis Mid-blastula Transition. Dev Cell. 2017;42:82-96.e3 pubmed publisher
    ..This study defines the downregulation of Drf1 as an important mechanism to coordinate the lengthening of the cell cycle and subsequent developmental processes. ..