Genomes and Genes
checkpoint kinase 2
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.
- 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. ..
- 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 ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- Chan K, Alonso NuÃ±ez 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. ..
- Pennisi R, Antoccia A, Leone S, Ascenzi P, di Masi A. Hsp90Î± 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 Hsp90Î± on the DDR, controlling ATM and NBN stability and influencing the DSBs signaling and repair. ..
- 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. ..
- 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 ..