Genomes and Genes
dna activated protein kinase
Summary: A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.
- Delia D, Fontanella E, Ferrario C, Chessa L, Mizutani S. DNA damage-induced cell-cycle phase regulation of p53 and p21waf1 in normal and ATM-defective cells. Oncogene. 2003;22:7866-9 pubmed
- Zou W, Che J, Wang C, Cui Y, Zhang Q. [DNA-PKcs silencing inhibit the DNA repair induced by low dose radiation on human breast epithelial cells]. Sheng Wu Gong Cheng Xue Bao. 2009;25:727-32 pubmed..The results suggested that DNA-PKcs gene silencing could increase the sensitivity of human breast epithelial cells to the LDR, which might be relative with the decrease of the proteins. ..
- Stephan H, Concannon C, Kremmer E, Carty M, Nasheuer H. Ionizing radiation-dependent and independent phosphorylation of the 32-kDa subunit of replication protein A during mitosis. Nucleic Acids Res. 2009;37:6028-41 pubmed publisher..Our data also indicate that the RPA2 hyperphosphorylation in response to IR is facilitated by the activity of both ATM and DNA-PK, and is associated with activation of the Chk2 pathway. ..
- Poplawski T, Blasiak J. BCR/ABL downregulates DNA-PK(CS)-dependent and upregulates backup non-homologous end joining in leukemic cells. Mol Biol Rep. 2010;37:2309-15 pubmed publisher..We suggest that BCR/ABL switch on B-NHEJ which is more error-prone then D-NHEJ and in such manner contribute to the increase of the genomic instability of leukemic cells. ..
- Britton S, Frit P, Biard D, Salles B, Calsou P. ARTEMIS nuclease facilitates apoptotic chromatin cleavage. Cancer Res. 2009;69:8120-6 pubmed publisher..These results show a facilitating role for ARTEMIS at least in early, site-specific chromosome breakage during apoptosis. ..
- Sakurai Y, Komatsu K, Agematsu K, Matsuoka M. DNA double strand break repair enzymes function at multiple steps in retroviral infection. Retrovirology. 2009;6:114 pubmed publisher..These results suggest that DSB repair enzymes are involved in multiple steps including integration and pre-integration steps during retroviral replication. ..
- Kobayashi J, Kato A, Ota Y, Ohba R, Komatsu K. Bisbenzamidine derivative, pentamidine represses DNA damage response through inhibition of histone H2A acetylation. Mol Cancer. 2010;9:34 pubmed publisher..These results indicate that inhibition of Tip60 as well as hMRE11 nuclease by pentamidine underlies the radiosensitizing effects of this compound making it an excellent sensitizer for radiotherapy or chemotherapy. ..
- Chen H, Lu H, Yang J, Kuo S, Lo C, Yang M, et al. The novel quinolone CHM-1 induces DNA damage and inhibits DNA repair gene expressions in a human osterogenic sarcoma cell line. Anticancer Res. 2010;30:4187-92 pubmed..Taken together, the results indicate that CHM-1 caused DNA damage and reduced DNA repair genes in U-2 OS cells, which may be the mechanism for CHM-1-inhibited cell growth and induction of apoptosis. ..
- Xiong H, Li S, Yang Z, Burgess R, Dynan W. E. coli expression of a soluble, active single-chain antibody variable fragment containing a nuclear localization signal. Protein Expr Purif. 2009;66:172-80 pubmed publisher..Following lipid-mediated uptake into cultured cells, NLS-tagged ScFv 18-2, unlike the parental ScFv 18-2, localized predominantly in the cell nucleus. ..
- Nock A, Ascano J, Jones T, Barrero M, Sugiyama N, Tomita M, et al. Identification of DNA-dependent protein kinase as a cofactor for the forkhead transcription factor FoxA2. J Biol Chem. 2009;284:19915-26 pubmed publisher..We therefore conclude that DNA-PK-dependent phosphorylation of FoxA2 plays a critical role in its transcriptional activation function per se. ..
- Saitou K, Mizumoto K, Nishimura T, Kai C, Tsukiyama Kohara K. Hepatitis C virus-core protein facilitates the degradation of Ku70 and reduces DNA-PK activity in hepatocytes. Virus Res. 2009;144:266-71 pubmed publisher..Therefore, it appears that the HCV-core protein facilitates the degradation of Ku70 and reduces DNA-PK activity in noncancerous liver cells. ..
- CallÃ©n E, Jankovic M, Wong N, Zha S, Chen H, Difilippantonio S, et al. Essential role for DNA-PKcs in DNA double-strand break repair and apoptosis in ATM-deficient lymphocytes. Mol Cell. 2009;34:285-97 pubmed publisher..Our experiments reveal a DNA-PKcs-dependent pathway that regulates DNA repair and activation of p53 in the absence of ATM. ..
- Du L, Zhou L, Pan X, Wang Y, Xu Q, Yang Z, et al. Radiosensitization and growth inhibition of cancer cells mediated by an scFv antibody gene against DNA-PKcs in vitro and in vivo. Radiat Oncol. 2010;5:70 pubmed publisher..The antiproliferation and radiosensitizing effects of anti-DPK3-scFv via targeting DNA-PKcs make it very appealing for the development as a novel biological radiosensitizer for cancer therapeutic potential. ..
- An J, Huang Y, Xu Q, Zhou L, Shang Z, Huang B, et al. DNA-PKcs plays a dominant role in the regulation of H2AX phosphorylation in response to DNA damage and cell cycle progression. BMC Mol Biol. 2010;11:18 pubmed publisher..It can directly phosphorylate H2AX independent of ATM and indirectly modulate the phosphorylation level of gamma H2AX via the Akt/GSK3 beta signal pathway. ..
- McCord R, Michishita E, Hong T, Berber E, Boxer L, Kusumoto R, et al. SIRT6 stabilizes DNA-dependent protein kinase at chromatin for DNA double-strand break repair. Aging (Albany NY). 2009;1:109-21 pubmed
- Bombarde O, Boby C, Gomez D, Frit P, Giraud Panis M, Gilson E, et al. TRF2/RAP1 and DNA-PK mediate a double protection against joining at telomeric ends. EMBO J. 2010;29:1573-84 pubmed publisher..Thus, telomeres are protected against EJ by a lock with two bolts. These results account for observations with mammalian models and underline the importance of alternative non-classical EJ pathways for telomere fusions in cells. ..
- Yano K, Morotomi Yano K, Adachi N, Akiyama H. Molecular mechanism of protein assembly on DNA double-strand breaks in the non-homologous end-joining pathway. J Radiat Res. 2009;50:97-108 pubmed..This new model provides important mechanistic insights into the protein assembly at DSBs and the regulation of DSB repair. ..
- Das B, Antony S, Gupta S, Dexheimer T, Redon C, Garfield S, et al. Optimal function of the DNA repair enzyme TDP1 requires its phosphorylation by ATM and/or DNA-PK. EMBO J. 2009;28:3667-80 pubmed publisher..Finally, we provide evidence that TDP1-S81 phosphorylation promotes cell survival and DNA repair in response to CPT-induced DSBs. Together; our findings provide a new mechanism for TDP1 post-translational regulation by ATM and DNA-PK. ..
- Britton S, Froment C, Frit P, Monsarrat B, Salles B, Calsou P. Cell nonhomologous end joining capacity controls SAF-A phosphorylation by DNA-PK in response to DNA double-strand breaks inducers. Cell Cycle. 2009;8:3717-22 pubmed..Addtionaly, the mapped phospho-site on SAF-A might serve as a potential bio-marker for DNA-PK activity in academic studies and clinical analyses of DNA-PK activators or inhibitors. ..
- White J, Choi S, Bakkenist C. Transient ATM kinase inhibition disrupts DNA damage-induced sister chromatid exchange. Sci Signal. 2010;3:ra44 pubmed publisher..This suggests that A-T fibroblasts have adapted to the loss of ATM and have alternative mechanisms to initiate SCE. ..
- Collaco R, Bevington J, Bhrigu V, Kalman Maltese V, Trempe J. Adeno-associated virus and adenovirus coinfection induces a cellular DNA damage and repair response via redundant phosphatidylinositol 3-like kinase pathways. Virology. 2009;392:24-33 pubmed publisher..However, AAV DNA levels are moderately affected by kinase inhibition. These experiments provide new insights into the cellular responses to AAV/Ad coinfections. ..
- Pawelczak K, Turchi J. Purification and characterization of exonuclease-free Artemis: Implications for DNA-PK-dependent processing of DNA termini in NHEJ-catalyzed DSB repair. DNA Repair (Amst). 2010;9:670-7 pubmed publisher..These data demonstrate that the exonuclease activity thought to be intrinsic to Artemis can be biochemically separated from the Artemis endonuclease. ..
- Gangwar R, Ahirwar D, Mandhani A, Mittal R. Do DNA repair genes OGG1, XRCC3 and XRCC7 have an impact on susceptibility to bladder cancer in the North Indian population?. Mutat Res. 2009;680:56-63 pubmed publisher..XRCC7 G allele carriers (TG+GG) are also at an elevated risk for susceptibility to UBC as evidenced by a high odds ratio throughout the analysis. ..
- Rajagopalan S, Moyle M, Joosten I, Long E. DNA-PKcs controls an endosomal signaling pathway for a proinflammatory response by natural killer cells. Sci Signal. 2010;3:ra14 pubmed publisher..The sequential requirement for DNA-PKcs, Akt, and NF-kappaB in signaling by CD158d delineates a previously uncharacterized endosomal signaling pathway for a proinflammatory response in NK cells. ..
- Mandal R, Kapoor R, Mittal R. Polymorphic variants of DNA repair gene XRCC3 and XRCC7 and risk of prostate cancer: a study from North Indian population. DNA Cell Biol. 2010;29:669-74 pubmed publisher..Our results strongly support that common sequence variants (GG) genotype of XRCC7 may increase risk of PCa. G allele being a risk allele in our study also suggests that this polymorphism be used as a marker for the PCa susceptibility. ..
- Economopoulou P, Pappa V, Kontsioti F, Papageorgiou S, Foukas P, Liakata E, et al. Expression analysis of proteins involved in the non homologous end joining DNA repair mechanism, in the bone marrow of adult de novo myelodysplastic syndromes. Ann Hematol. 2010;89:233-9 pubmed publisher..04). Our findings suppor-t a potential role of NHEJ enzyme Ligase IV in the pathogenesis of MDS. Larger numbers of cases need to be screened in order to draw definite conclusion. ..
- Sharma G, So S, Gupta A, Kumar R, Cayrou C, Avvakumov N, et al. MOF and histone H4 acetylation at lysine 16 are critical for DNA damage response and double-strand break repair. Mol Cell Biol. 2010;30:3582-95 pubmed publisher..We propose that MOF, through H4K16ac (histone code), has a critical role at multiple stages in the cellular DNA damage response and DSB repair. ..
- Berglund F, Clarke P. hnRNP-U is a specific DNA-dependent protein kinase substrate phosphorylated in response to DNA double-strand breaks. Biochem Biophys Res Commun. 2009;381:59-64 pubmed publisher..We show that hnRNP-U is phosphorylated at Ser59 by DNA-PK in vitro and in cells in response to DNA double-strand breaks. Phosphorylation of hnRNP-U suggests novel functions for DNA-PK in the response to DNA damage. ..
- Taylor E, Cecillon S, Bonis A, Chapman J, Povirk L, Lindsay H. The Mre11/Rad50/Nbs1 complex functions in resection-based DNA end joining in Xenopus laevis. Nucleic Acids Res. 2010;38:441-54 pubmed publisher..These data indicate a role for the X. laevis MRN complex in MMEJ. ..
- Cano C, Golding B, Haggerty K, Hardcastle I, Peacock M, Griffin R. Atropisomeric 8-arylchromen-4-ones exhibit enantioselective inhibition of the DNA-dependent protein kinase (DNA-PK). Org Biomol Chem. 2010;8:1922-8 pubmed publisher..Biological evaluation against DNA-PK of the pairs of atropisomers showed a marked difference in potency, with only one enantiomer being biologically active. ..
- Schwartz R, Carson C, Schuberth C, Weitzman M. Adeno-associated virus replication induces a DNA damage response coordinated by DNA-dependent protein kinase. J Virol. 2009;83:6269-78 pubmed publisher..Our results demonstrate that AAV replication in the presence of Ad helper functions elicits a unique damage response controlled by DNA-PK. ..
- Fan J, Huang T, Wen C, Shen T, Li T. Sodium salicylate acts through direct inhibition of phosphoinositide 3-kinase-like kinases to modulate topoisomerase-mediated DNA damage responses. Eur J Pharmacol. 2010;638:13-20 pubmed publisher..Together, our study provides evidence that NSAIDs exhibit a novel COX-independent modulating activity of NSAIDs on the DNA damage responses and it is through inhibition of phosphoinositide 3-kinase-like kinases. ..
- Chen Y, Chiang S, Lin J, Yang J, Ma Y, Liao C, et al. Emodin, aloe-emodin and rhein induced DNA damage and inhibited DNA repair gene expression in SCC-4 human tongue cancer cells. Anticancer Res. 2010;30:945-51 pubmed..In conclusion, these agents induced DNA damage followed by the inhibition of DNA repair-associated gene expressions, including ATM, ATR, 14-3-3sigma, BRCA1, DNA-PK and MGMT in SCC-4 human tongue cancer cells. ..
- Daya S, Cortez N, Berns K. Adeno-associated virus site-specific integration is mediated by proteins of the nonhomologous end-joining pathway. J Virol. 2009;83:11655-64 pubmed publisher..Together, these data suggest that NHEJ proteins participate in site-specific integration, and indicate a role for the single-stranded form of AAV DNA in targeted integration. ..
- Medunjanin S, Weinert S, Schmeisser A, Mayer D, Braun Dullaeus R. Interaction of the double-strand break repair kinase DNA-PK and estrogen receptor-alpha. Mol Biol Cell. 2010;21:1620-8 pubmed publisher..Activation of DNA-PK by double-strand breaks or its inhibition by siRNA technology demonstrated that estrogen-induced ERalpha activation and cell cycle progression is, at least, partially dependent on DNA-PK. ..
- Mannell H, Hammitzsch A, Mettler R, Pohl U, Krotz F. Suppression of DNA-PKcs enhances FGF-2 dependent human endothelial cell proliferation via negative regulation of Akt. Cell Signal. 2010;22:88-96 pubmed publisher..Our findings indicate DNA-PK as an important enzyme maintaining the quiescent endothelial phenotype by actively inhibiting Akt thus restraining endothelial cell proliferation preventing excessive growth. ..
- Kim S, Lim D, Canman C, Kastan M. Substrate specificities and identification of putative substrates of ATM kinase family members. J Biol Chem. 1999;274:37538-43 pubmed..Brca2, phosphatidylinositol 3-kinase, and DNA-5B peptides were phosphorylated specifically by ATR, and DNA Ligase IV is a specific in vitro substrate of DNA-PK. ..
- Orsburn B, Escudero B, Prakash M, Gesheva S, Liu G, Huso D, et al. Differential requirement for H2AX and 53BP1 in organismal development and genome maintenance in the absence of poly(ADP)ribosyl polymerase 1. Mol Cell Biol. 2010;30:2341-52 pubmed publisher..These findings have important implications for our understanding of the mechanisms whereby ATM-regulated DDR prevents human aging and cancer. ..
- Kanungo J. Gradual loss of DNA-PK activity from the cytoplasm is coincident with the nuclear translocation of its activator Ku during early development of Xenopus laevis. Folia Biol (Praha). 2009;55:218-23 pubmed
- Wong R, Chang I, Hudak C, Hyun S, Kwan H, Sul H. A role of DNA-PK for the metabolic gene regulation in response to insulin. Cell. 2009;136:1056-72 pubmed publisher..Our study demonstrates that a kinase central to the DNA damage response mediates metabolic gene activation. ..
- Meador J, Su Y, Ravanat J, Balajee A. DNA-dependent protein kinase (DNA-PK)-deficient human glioblastoma cells are preferentially sensitized by Zebularine. Carcinogenesis. 2010;31:184-91 pubmed publisher..Collectively, our study suggests that DNA-PK is the major determining factor for cellular response to Zebularine. ..
- Cao R, Zeng H, Zhang H. 3D-QSAR studies on a series of inhibitors docked into a new homology model of the DNA-PK receptor. Curr Pharm Des. 2009;15:3796-825 pubmed..503, r(2) =0.870). Our models would offer help to better comprehend the structure-activity relationship existent for this class of compounds and also facilitate the design of new inhibitors with good chemical derivsity. ..
- Zhou T, Akopiants K, Mohapatra S, Lin P, Valerie K, Ramsden D, et al. Tyrosyl-DNA phosphodiesterase and the repair of 3'-phosphoglycolate-terminated DNA double-strand breaks. DNA Repair (Amst). 2009;8:901-11 pubmed publisher..This chromosomal hypersensitivity, as well as a small but reproducible enhancement of calicheamicin cytotoxicity following siRNA-mediated TDP1 knockdown, suggests a role for TDP1 in repair of 3'-PG double-strand breaks in vivo. ..
- Bi Y, Li Y, Kong M, Xiao X, Zhao Z, He X, et al. Gene expression in benzene-exposed workers by microarray analysis of peripheral mononuclear blood cells: induction and silencing of CYP4F3A and regulation of DNA-dependent protein kinase catalytic subunit in DNA double strand break repair. Chem Biol Interact. 2010;184:207-11 pubmed publisher..Induction of the genes may play a role in the pathogenesis of benzene hematotoxicity and serve as biomarkers of benzene exposure. ..
- Urano M, He F, Minami A, Ling C, Li G. Response to multiple radiation doses of human colorectal carcinoma cells infected with recombinant adenovirus containing dominant-negative Ku70 fragment. Int J Radiat Oncol Biol Phys. 2010;77:877-85 pubmed publisher..Infection of recombinant replication-defective adenovirus containing dominant-negative Ku70 fragment enhanced the response of human colorectal cancer cells to single and multiple radiation doses. ..
- Ohno M, Kunimoto M, Nishizuka M, Osada S, Imagawa M. Ku proteins function as corepressors to regulate farnesoid X receptor-mediated gene expression. Biochem Biophys Res Commun. 2009;390:738-42 pubmed publisher..Furthermore, we demonstrated that ectopic expression of the Ku proteins decreased the promoter activity and expression of BSEP gene mediated by FXR. These results suggest that the Ku proteins function as corepressors for FXR...
- Yan D, Ng W, Zhang X, Wang P, Zhang Z, Mo Y, et al. Targeting DNA-PKcs and ATM with miR-101 sensitizes tumors to radiation. PLoS ONE. 2010;5:e11397 pubmed publisher..These data demonstrate for the first time that miRNAs could be used to target DNA repair genes and thus sensitize tumors to radiation. These results provide a new way for improving tumor radiotherapy. ..
- Johns T, McKay M, Cvrljevic A, Gan H, Taylor C, Xu H, et al. MAb 806 enhances the efficacy of ionizing radiation in glioma xenografts expressing the de2-7 epidermal growth factor receptor. Int J Radiat Oncol Biol Phys. 2010;78:572-8 pubmed publisher..We have previously shown that mAb 806, a novel EGFR-specific antibody, is able to inhibit the growth of U87MG.?2-7 glioma xenografts expressing the de2-7 EGFR and may have potential as a therapeutic...
- Li A, Boo L, Wang S, Lin H, Wang C, Yen Y, et al. Suppression of nonhomologous end joining repair by overexpression of HMGA2. Cancer Res. 2009;69:5699-706 pubmed publisher..In summary, a novel role for HMGA2 to interfere with NHEJ processes was uncovered, implicating HMGA2 in the promotion of genome instability and tumorigenesis. ..
- Quanz M, Chassoux D, Berthault N, Agrario C, Sun J, Dutreix M. Hyperactivation of DNA-PK by double-strand break mimicking molecules disorganizes DNA damage response. PLoS ONE. 2009;4:e6298 pubmed publisher..Together, our results suggest that the hyperactivation of DNA-PK is insufficient for complete execution of the DDR but induces a "false" DNA damage signaling that disorganizes the DNA repair system. ..
- Haykal J, Geara F, Haddadin M, Smith C, Gali Muhtasib H. The radiosensitizer 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide induces DNA damage in EMT-6 mammary carcinoma cells. Radiat Oncol. 2009;4:25 pubmed publisher..Collectively, our findings indicate that radiosensitization by DCQ is mediated by DNA damage and decreased repair and that ROS are at least partially responsible. ..