keyword
MENU ▼
Read by QxMD icon Read
search

Dna-pk

keyword
https://www.readbyqxmd.com/read/28070830/mesenchymal-subtype-of-glioblastomas-with-high-dna-pkcs-expression-is-associated-with-better-response-to-radiotherapy-and-temozolomide
#1
Baptiste Pinel, Mathilde Duchesne, Julie Godet, Serge Milin, Antoine Berger, Michel Wager, Lucie Karayan-Tapon
A better understanding of the relationship between glioblastomas molecular subtypes and radio-chemotherapy is needed for the development of individualized strategies. In this study, we aimed to assess whether non-homologous end-joining (NHEJ) protein expression is associated and could predict responses to treatment of mesenchymal (MES) and proneural (PN) subtypes. Tumors from 122 patients with a glioblastoma treated at the University Hospital of Poitiers between 2002-2013 by an association of radiotherapy and temozolomide were collected...
January 10, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28051062/paxx-promotes-ku-accumulation-at-dna-breaks-and-is-essential-for-end-joining-in-xlf-deficient-mice
#2
Xiangyu Liu, Zhengping Shao, Wenxia Jiang, Brian J Lee, Shan Zha
Non-homologous end-joining (NHEJ) is the most prominent DNA double strand break (DSB) repair pathway in mammalian cells. PAXX is the newest NHEJ factor, which shares structural similarity with known NHEJ factors-XRCC4 and XLF. Here we report that PAXX is dispensable for physiological NHEJ in otherwise wild-type mice. Yet Paxx(-/-) mice require XLF and Xlf(-/-) mice require PAXX for end-ligation. As such, Xlf(-/-)Paxx(-/-) mice display severe genomic instability and neuronal apoptosis, which eventually lead to embryonic lethality...
January 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28034453/dna-damage-repair-in-breast-cancer-and-its-therapeutic-implications
#3
REVIEW
Reem Ali, Emad A Rakha, Srinivasan Madhusudan, Helen E Bryant
The DNA damage response (DDR) involves the activation of numerous cellular activities that repair DNA lesions and maintain genomic integrity, and is critical in preventing tumorigenesis. Inherited or acquired mutations in specific genes involved in the DNA damage response, for example the breast cancer susceptibility genes 1/2 (BRCA1/2), phosphatase and tensin homolog (PTEN) and P53 are associated with various subtypes of breast cancer. Such changes can render breast cancer cells particularly sensitive to specific DNA damage response inhibitors, for example BRCA1/2 germline mutated cells are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors...
December 26, 2016: Pathology
https://www.readbyqxmd.com/read/28011258/identification-of-kinases-phosphorylating-13-sites-in-the-nuclear-dna-binding-protein-nucks
#4
Kirsten Grundt, Bernd Thiede, Anne Carine Østvold
NUCKS is a vertebrate specific, nuclear and DNA-binding phospho protein. The protein is highly expressed in rapidly dividing cells, and is overexpressed in a number of cancer tissues. The phosphorylation of NUCKS is cell cycle and DNA-damage regulated, but little is known about the responsible kinases. By utilizing in vitro and in vivo phosphorylation assays using isolated NUCKS as well as synthetic NUCKS-derived peptides in combination with mass spectrometry, phosphopeptide mapping, phosphphoamino acid analyses, phosphospecific antibodies and the use of specific kinase inhibitors, we found that NUCKS is phosphorylated on 11 sites by CK2...
December 21, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27982097/induction-of-a-cellular-dna-damage-response-by-porcine-circovirus-type-2-facilitates-viral-replication-and-mediates-apoptotic-responses
#5
Li Wei, Shanshan Zhu, Jing Wang, Rong Quan, Xu Yan, Zixue Li, Lei Hou, Naidong Wang, Yi Yang, Haijun Jiang, Jue Liu
Cellular DNA damage response (DDR) triggered by infection of DNA viruses mediate cell cycle checkpoint activation, DNA repair, or apoptosis induction. In the present study, infection of porcine circovirus type 2 (PCV2), which serves as a major etiological agent of PCV2-associated diseases (PCVAD), was found to elicit a DNA damage response (DDR) as observed by the phosphorylation of H2AX and RPA32 following infection. The response requires active viral replication, and all the ATM (ataxia telangiectasia-mutated kinase), ATR (ATM- and Rad3-related kinase), and DNA-PK (DNA-dependent protein kinase) are the transducers of the DDR signaling events in the PCV2-infected cells as demonstrated by the phosphorylation of ATM, ATR, and DNA-PK signalings as well as reductions in their activations after treatment with specific kinase inhibitors...
December 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27935869/the-involvement-of-bcl-2-family-proteins-in-akt-regulated-cell-survival-in-cisplatin-resistant-epithelial-ovarian-cancer
#6
Yan Dai, Shiguang Jin, Xueping Li, Daxin Wang
Many studies involving patients with cisplatin-resistant ovarian cancer have shown that AKT activation leads to inhibition of apoptosis. The aim of this study was to examine the potential involvement of the Bcl-2 family proteins in AKT-regulated cell survival in response to cisplatin treatment. Cisplatin-sensitive (PEO1) and cisplatin-resistant (PEO4) cells were taken from ascites of patients with ovarian cancer before cisplatin treatment and after development of chemoresistance. It was found that cisplatin treatment activated the AKT signaling pathway and promoted cell proliferation in cisplatin-resistant EOC cells...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27887917/microrna-136-inhibits-cancer-stem-cell-activity-and-enhances-the-anti-tumor-effect-of-paclitaxel-against-chemoresistant-ovarian-cancer-cells-by-targeting-notch3
#7
Ju-Yeon Jeong, Haeyoun Kang, Tae Hoen Kim, Gwangil Kim, Jin-Hyung Heo, Ah-Young Kwon, Sewha Kim, Sang-Geun Jung, Hee-Jung An
To identify microRNAs (miRNAs) regulating Notch3 expression in association with paclitaxel resistance, candidate miRNAs targeting Notch3 were predicted using TargetScan. We found that miR-136 directly targets Notch3, and miR-136 was significantly downregulated in OSC tissues relative to normal control tissues, and low expression of miR-136 correlated with poor overall in ovarian cancer patients. Artificial miR-136 overexpression significantly reduced cell viability, proliferation, Cancer stem cell (CSC) spheroid formation, and angiogenesis, and increased apoptosis in paclitaxel-resistant SKpac cells compared with the effects of paclitaxel alone...
February 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27875301/an-intrinsically-disordered-aplf-links-ku-dna-pkcs-and-xrcc4-dna-ligase-iv-in-an-extended-flexible-non-homologous-end-joining-complex
#8
Michal Hammel, Yaping Yu, Sarvan K Radhakrishnan, Chirayu Chokshi, Miaw-Sheue Tsai, Yoshihiro Matsumoto, Monica Kuzdovich, Soumya G Remesh, Shujuan Fang, Alan E Tomkinson, Susan P Lees-Miller, John A Tainer
DNA double-strand break (DSB) repair by non-homologous end joining (NHEJ) in human cells is initiated by Ku heterodimer binding to a DSB, followed by recruitment of core NHEJ factors including DNA-dependent protein kinase catalytic subunit (DNA-PKcs), XRCC4-like factor (XLF), and XRCC4 (X4)-DNA ligase IV (L4). Ku also interacts with accessory factors such as aprataxin and polynucleotide kinase/phosphatase-like factor (APLF). Yet, how these factors interact to tether, process, and ligate DSB ends while allowing regulation and chromatin interactions remains enigmatic...
December 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27829214/pict-1-is-a-key-nucleolar-sensor-in-dna-damage-response-signaling-that-regulates-apoptosis-through-the-rpl11-mdm2-p53-pathway
#9
Hongbo Chen, Liqiao Han, Hsiangi Tsai, Zhiwei Wang, Yanping Wu, Yanhong Duo, Wei Cao, Lijun Chen, Zhirong Tan, Ning Xu, Xianzhang Huang, Junhua Zhuang, Laiqiang Huang
PICT-1 is an essential ribosome biogenesis factor whose loss induces p53 accumulation and apoptosis. Here, we show that DNA damage changes PICT-1 localization and decreases PICT-1 protein levels via the proteasome pathway. Two important phosphatidylinositol 3-kinase-like kinases (PIKKs), ataxia-telangiectasia mutated (ATM) and the Ku70 subunit of DNA-dependent protein kinase (DNA-PK), co-localize and interact with PICT-1 in the nucleolus. Computational prediction of phosphorylation sites and detection using an anti-phospho-substrate antibody suggest that PICT-1 might be a substrate of PIKKs...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27813122/quercetin-alters-the-dna-damage-response-in-human-hematopoietic-stem-and-progenitor-cells-via-topoii-and-pi3k-dependent-mechanisms-synergizing-in-leukemogenic-rearrangements
#10
Shahar Biechonski, Dana Gourevich, Melanie Rall, Nasma Aqaqe, Muhammad Yassin, Adi Zipin-Roitman, Luba Trakhtenbrot, Leonid Olender, Yael Raz, Ariel J Jaffa, Dan Grisaru, Lisa Wiesmuller, David Elad, Michael Milyavsky
Quercetin (Que) is an abundant flavonoid in the human diet and high-concentration food supplement with reported pro- and anti-carcinogenic activities. Topoisomerase II (TopoII) inhibition and subsequent DNA damage induction by Que was implicated in the mixed lineage leukemia gene (MLL) rearrangements that can induce infant and adult leukemias. This notion raised concerns regarding possible genotoxicities of Que in hematopoietic stem and progenitor cells (HSPCs). However, molecular targets mediating Que effects on DNA repair relevant to MLL translocations have not been defined...
February 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27776457/homologous-recombination-preferentially-repairs-heat-induced-dna-double-strand-breaks-in-mammalian-cells
#11
Akihisa Takahashi, Eiichiro Mori, Yosuke Nakagawa, Atsuhisa Kajihara, Tadaaki Kirita, L Pittman Douglas, Masatoshi Hasegawa, Takeo Ohnishi
PURPOSE: Heat shock induces DNA double-strand breaks (DSBs), but the precise mechanism of repairing heat-induced damage is unclear. Here, we investigated the DNA repair pathways involved in cell death induced by heat shock. MATERIALS AND METHODS: B02, a specific inhibitor of human RAD51 (homologous recombination; HR), and NU7026, a specific inhibitor of DNA-PK (non-homologous end-joining; NHEJ), were used for survival assays of human cancer cell lines with different p53-gene status...
October 24, 2016: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/27765510/synthesis-of-linear-and-angular-aryl-morpholino-naphth-oxazines-their-dna-pk-pi3k-pde3a-and-antiplatelet-activity
#12
Rick Morrison, Zhaohua Zheng, Ian G Jennings, Philip E Thompson, Jasim M A Al-Rawi
To continue our study of 2-morpholino-benzoxazine based compounds, which show useful activity against PI3K family enzymes or antiplatelet activity, we designed and synthesized a series of linear 6.7-fused, 5,6-angular fused and 7,8-angular fused-aryl-morpholino-naphth-oxazines. The compounds were prepared from substituted 2-hydroxynaphthoic acid to give the corresponding thioxo analogues 8, 9, 15 and 19. The thioxo products were then converted to the morpholino substituted analogue. The aryl group was introduced by Suzuki coupling of bromo precursors...
November 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27764514/sirtuins-and-their-interactions-with-transcription-factors-and-poly-adp-ribose-polymerases
#13
H Jęśko, R P Strosznajder
Sirtuins (SIRT1 to -7) are unique histone deacetylases (HDACs) whose activity depends on NAD+, thus making them capable of sensing the cellular metabolic status. Sirtuins orchestrate the stress response and damage repair, and are able to modulate the course of ageing and neurodegenerative diseases. Despite their classification as HDACs, sirtuins deacetylate a vast number of targets in many cellular compartments, and some display additional enzymatic activities including mono(ADP-ribosyl)ation. SIRTs interact with multiple signalling proteins, transcription factors and enzymes including p53, FOXOs (forkhead box subgroup O), PPARs (peroxisome proliferator-activated receptors), NF-B, and DNA-PK (DNA-dependent protein kinase)...
2016: Folia Neuropathologica
https://www.readbyqxmd.com/read/27723831/the-architectural-chromatin-factor-high-mobility-group-a1-enhances-dna-ligase-iv-activity-influencing-dna-repair
#14
Ilenia Pellarin, Laura Arnoldo, Silvia Costantini, Silvia Pegoraro, Gloria Ros, Carlotta Penzo, Gianluca Triolo, Francesca Demarchi, Riccardo Sgarra, Alessandro Vindigni, Guidalberto Manfioletti
The HMGA1 architectural transcription factor is an oncogene overexpressed in the vast majority of human cancers. HMGA1 is a highly connected node in the nuclear molecular network and the key aspect of HMGA1 involvement in cancer development is that HMGA1 simultaneously confers cells multiple oncogenic hits, ranging from global chromatin structural and gene expression modifications up to the direct functional alterations of key cellular proteins. Interestingly, HMGA1 also modulates DNA damage repair pathways...
2016: PloS One
https://www.readbyqxmd.com/read/27702817/ovarian-cancers-harbour-defects-in-non-homologous-end-joining-resulting-in-resistance-to-rucaparib
#15
Aiste McCormick, Peter Donoghue, Michelle Dixon, Richard O'Sullivan, Rachel Louise O'Donnell, James Murray, Angelika Kaufmann, Nicola J Curtin, Richard J Edmondson
PURPOSE: DNA damage defects are common in ovarian cancer and can be used to stratify treatment. Although most work has focussed on Homologous Recombination (HR), DNA double strand breaks are repaired primarily by non-homologous end joining (NHEJ). Defects in NHEJ have been shown to contribute to genomic instability and have been associated with the development of chemoresistance. EXPERIMENTAL DESIGN: NHEJ was assessed in a panel of ovarian cancer cell lines and 47 primary ascitic derived ovarian cancer cultures, by measuring the ability of cell extracts to end-join linearized plasmid monomers into multimers...
October 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27693461/inhibition-of-atr-dependent-feedback-activation-of-chk1-sensitises-cancer-cells-to-chk1-inhibitor-monotherapy
#16
Andrew J Massey
The Chk1 and ATR kinases are critical mediators of the DNA damage response pathway and help protect cancer cells from endogenous and oncogene induced replication stress. Inhibitors of both kinases are currently being evaluated in clinical trials. Chk1 inhibition with V158411 increases DNA damage and activates the ATR, ATM and DNA-PKcs dependent DNA damage response pathways. Inhibiting ATR, ATM and/or DNA-PKcs has the potential to increase the therapeutic activity of Chk1 inhibitors. ATR inhibition but not ATM or DNA-PKcs inhibition potentiated the cytotoxicity of V158411 in p53 mutant and wild type human cancer cell lines...
September 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27690730/chk1-and-dna-pk-mediate-tpen-induced-dna-damage-in-a-ros-dependent-manner-in-human-colon-cancer-cells
#17
Omar Nasser Rahal, Maamoun Fatfat, Carla Hankache, Bassam Osman, Hala Khalife, Khaled Machaca, Hala-Gali Muhtasib
Recently, we showed that the metal chelator TPEN targets colon cancer cells through redox cycling of copper. Here, we studied the DNA damage potential of TPEN and deciphered the role of Chk1, ATM and DNA-PK in TPEN-induced toxicity in 3 human colon cancer cell lines, HCT116, SW480 and HT29. We also investigated the role of reactive oxygen species (ROS) in TPEN-induced DNA damage. TPEN reduced cell viability in a dose- and time-dependent manner. Cytotoxicity was associated with significant DNA damage and higher expression of γ-H2AX protein and activation of ATM/ATR signaling pathway...
November 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27675958/rnf8-regulates-nonhomologous-end-joining-and-dna-pk-recruitment-to-dna-double-strand-break-sites
#18
S Gao, Y Surovtseva, R S Bindra
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27668603/-role-of-dna-dependent-protein-kinase-in-the-hiv-1-replication-cycle
#19
E S Knyazhanskaya, O A Shadrina, A N Anisenko, M B Gottikh
Human immunodeficiency virus type 1 (HIV-1) is among the best-studied viruses, but some aspects of HIV-1 biology remain obscure. The role of cell proteins in virus replication raises especially many questions. One of the proteins is DNA-dependent protein kinase (DNA-PK), which performs crucially important functions in the human body. DNA-PK is known to influence at least two stages in the HIV-1 life cycle, the integration of viral genome in cell DNA and transcription of the integrated provirus. Many details regarding this influence remain unresolved...
July 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27643582/comparison-of-the-radiosensitizing-effect-of-atr-atm-and-dna-pk-kinase-inhibitors-on-cervical-carcinoma-cells
#20
J Vávrová, L Zárybnická, P Jošt, A Tichý, M Řezáčová, Z Šinkorová, J Pejchal
Here, we compared the effects of inhibitors of three phosphatidylinositol-3-kinase-related kinases, ATM, ATR a DNA-PK, on radiosensitization of cervical carcinoma cells. We demonstrated that DNA-PK inhibitor NU7441 enhanced phosphorylation of Chk1 and Chk2 kinases 2 h after irradiation of HeLa cells at a dose of 8 Gy in contrast to ATM kinase inhibitor KU55933, which completely blocked the Chk2 kinase phosphorylation on threonine 68, and ATR kinase inhibitor VE-821, which blocked the Chk1 kinase phosphorylation on serine 345...
2016: Folia Biologica (Praha)
keyword
keyword
39359
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"