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https://www.readbyqxmd.com/read/27922110/%C3%AE-h2ax-53bp1-pkap-1-foci-and-their-linear-tracks-induced-by-in-vitro-exposure-to-radon-and-its-progeny-in-human-peripheral-blood-lymphocytes
#1
Defang Ding, Yaping Zhang, Jing Wang, Xufei Wang, Dunhuang Fan, Linfeng He, Xuxia Zhang, Yun Gao, Qiang Li, Honghong Chen
The biodosimetric information is critical for evaluating the human health hazards caused by radon and its progeny. Here, we demonstrated that the formation of phosphorylated histone variant H2AX (γ-H2AX), p53-binding protein 1 (53BP1) and phosphorylated KRAB-associated protein 1 (pKAP-1) foci and their linear tracks in human peripheral blood lymphocytes (HPBLs) in vitro exposed to radon and its progeny were dependent on the cumulative absorbed dose of radon exposure but was unrelated to the concentration of radon...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27903633/an-e2-guided-e3-screen-identifies-the-rnf17-ube2u-pair-as-regulator-of-the-riddle-syndrome-protein-rnf168
#2
Yingying Guo, Liwei An, Hoi-Man Ng, Shirley M H Sy, Michael S Y Huen
Protein ubiquitination has emerged as pivotal regulatory reactions that promote cellular responses to DNA damage. With a goal to delineate the DNA damage signal transduction cascade, we systematically analysed the human E2 ubiquitin and ubiquitin-like conjugating enzymes for their ability to mobilise the DNA damage marker 53BP1 onto IR-induced DNA double-strand breaks (DSBs). RNAi-based screen identified UBE2U as a candidate regulator of chromatin responses at DSBs. Further mining of the UBE2U interactome uncovered its cognate E3 RNF17 as a novel factor that, via the Riddle syndrome protein RNF168, enforces DNA damage responses...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27899080/erratum-to-53bp1-depletion-causes-parp-inhibitor-resistance-in-atm-deficient-breast-cancer-cells
#3
Ruoxi Hong, Fei Ma, Weimin Zhang, Xiying Yu, Qing Li, Yang Luo, Changjun Zhu, Binghe Xu, Wei Jiang
No abstract text is available yet for this article.
November 30, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27893463/inhibition-of-the-gas6-axl-pathway-augments-the-efficacy-of-chemotherapies
#4
Mihalis S Kariolis, Yu Rebecca Miao, Anh Diep, Shannon E Nash, Monica M Olcina, Dadi Jiang, Douglas S Jones, Shiven Kapur, Irimpan I Mathews, Albert C Koong, Erinn B Rankin, Jennifer R Cochran, Amato J Giaccia
The AXL receptor and its activating ligand, growth arrest-specific 6 (GAS6), are important drivers of metastasis and therapeutic resistance in human cancers. Given the critical roles that GAS6 and AXL play in refractory disease, this signaling axis represents an attractive target for therapeutic intervention. However, the strong picomolar binding affinity between GAS6 and AXL and the promiscuity of small molecule inhibitors represent important challenges faced by current anti-AXL therapeutics. Here, we have addressed these obstacles by engineering a second-generation, high-affinity AXL decoy receptor with an apparent affinity of 93 femtomolar to GAS6...
November 28, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27866833/tp53-and-53bp1-reunited
#5
Thierry Soussi, Guido Kroemer
Identified as a TP53-binding protein, 53BP1 is a key regulator of the cellular response to double-strand breaks, a TP53-independent activity. Recent data have established a new TP53-dependent function for 53BP1 in mitotic surveillance after centrosome loss.
November 17, 2016: Trends in Cell Biology
https://www.readbyqxmd.com/read/27849008/ku70-serine-155-mediates-aurora-b-inhibition-and-activation-of-the-dna-damage-response
#6
Victoria L Fell, Elizabeth A Walden, Sarah M Hoffer, Stephanie R Rogers, Amelia S Aitken, Louisa M Salemi, Caroline Schild-Poulter
The Ku heterodimer (Ku70/Ku80) is the central DNA binding component of the classical non-homologous end joining (NHEJ) pathway that repairs DNA double-stranded breaks (DSBs), serving as the scaffold for the formation of the NHEJ complex. Here we show that Ku70 is phosphorylated on Serine 155 in response to DNA damage. Expression of Ku70 bearing a S155 phosphomimetic substitution (Ku70 S155D) in Ku70-deficient mouse embryonic fibroblasts (MEFs) triggered cell cycle arrest at multiple checkpoints and altered expression of several cell cycle regulators in absence of DNA damage...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27821478/mcl-1-depletion-impairs-dna-dsb-repair-and-re-initiation-of-stalled-dna-replication-forks
#7
Abid R Mattoo, Raj K Pandita, Sharmistha Chakraborty, Vijaya Charaka, Kalpana Mujoo, Clayton R Hunt, Tej K Pandita
Myeloid cell leukemia-1 : MCL-1) is a pro-survival BCL-2 protein family member highly expressed in hematopoietic stem cells (HSCs) and regulated by growth factor signals that manifest anti-apoptotic activity. Here we report that depletion of MCL-1, but not its isoform MCL1S, increases genomic instability and cell sensitivity to ionizing radiation (IR) induced death. MCL-1 association with genomic DNA increased post-irradiation and it co-localized with 53BP1 in foci. Post-irradiation, MCL-1 depleted cells exhibited decreased γ-H2AX foci, decreased phosphorylation of ATR and higher levels of residual 53BP1 and RIF1 foci, suggesting DNA DSB repair by homologous recombination (HR) was compromised...
November 7, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27820601/scai-promotes-dna-double-strand-break-repair-in-distinct-chromosomal-contexts
#8
Rebecca Kring Hansen, Andreas Mund, Sara Lund Poulsen, Maria Sandoval, Karolin Klement, Katerina Tsouroula, Maxim A X Tollenaere, Markus Räschle, Rebeca Soria, Stefan Offermanns, Thomas Worzfeld, Robert Grosse, Dominique T Brandt, Björn Rozell, Matthias Mann, Francesca Cole, Evi Soutoglou, Aaron A Goodarzi, Jeremy A Daniel, Niels Mailand, Simon Bekker-Jensen
DNA double-strand breaks (DSBs) are highly cytotoxic DNA lesions, whose accurate repair by non-homologous end-joining (NHEJ) or homologous recombination (HR) is crucial for genome integrity and is strongly influenced by the local chromatin environment. Here, we identify SCAI (suppressor of cancer cell invasion) as a 53BP1-interacting chromatin-associated protein that promotes the functionality of several DSB repair pathways in mammalian cells. SCAI undergoes prominent enrichment at DSB sites through dual mechanisms involving 53BP1-dependent recruitment to DSB-surrounding chromatin and 53BP1-independent accumulation at resected DSBs...
November 7, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27812868/detection-of-dysfunctional-telomeres-in-oncogene-induced-senescence
#9
Priyanka L Patel, Utz Herbig
Expressing oncogenes in normal somatic human cells leads to cellular senescence after just a few cell division cycles. In cells that are more resistant to culture stresses, such as human dermal fibroblasts, this oncogene-induced senescence (OIS) is a result of a DNA damage response (DDR) that is activated due to the formation of DNA lesions at both non-telomeric and telomeric DNA sequences. DNA lesions can be visualized as DDR foci by immunofluorescence microscopy using antibodies against a number of DDR factors, including ϒ-H2AX and 53BP1...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27798638/53bp1-protects-against-ctip-dependent-capture-of-ectopic-chromosomal-sequences-at-the-junction-of-distant-double-strand-breaks
#10
Josée Guirouilh-Barbat, Camille Gelot, Anyong Xie, Elodie Dardillac, Ralph Scully, Bernard S Lopez
DNA double-strand breaks (DSB) are very harmful lesions that can generate genome rearrangements. In this study, we used intrachromosomal reporters to compare both the efficiency and accuracy of end-joining occurring with close (34 bp apart) vs. distant DSBs (3200 bp apart) in human fibroblasts. We showed that a few kb between two intrachromosomal I-SceI-induced DSBs are sufficient to foster deletions and capture/insertions at the junction scar. Captured sequences are mostly coupled to deletions and can be partial duplications of the reporter (i...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27798234/nuclear-constriction-segregates-mobile-nuclear-proteins-away-from-chromatin
#11
Jerome Irianto, Charlotte R Pfeifer, Rachel R Bennett, Yuntao Xia, Irena L Ivanovska, Andrea J Liu, Roger A Greenberg, Dennis E Discher
As a cancer cell squeezes its nucleus through adjacent tissue, penetrates a basement membrane, or enters a small blood capillary, chromatin density and nuclear factors might be physically perturbed. Here, in cancer cell migration through rigid micropores and in passive pulling into micropipettes, local compaction of chromatin is observed coincident with depletion of mobile factors. Hetero/eu-chromatin has been previously estimated from molecular mobility measurements to occupy a volume fraction f that might be two-thirds of the nuclear volume, but based on the relative intensity of DNA and histones in several cancer cell lines drawn into narrow constrictions, f can easily increase locally to nearly 100%...
October 26, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27788492/targeting-enox1-in-tumor-stroma-increases-the-efficacy-of-fractionated-radiotherapy
#12
Clayton A Smith, Stacey Mont, Geri Traver, Konjeti R Sekhar, Peter A Crooks, Michael L Freeman
The goal of this investigation was to clarify the question of whether targeting Enox1 in tumor stroma would synergistically enhance the survival of tumor-bearing mice treated with fractionated radiotherapy. Enox1, a NADH oxidase, is expressed in tumor vasculature and stroma. However, it is not expressed in many tumor types, including HT-29 colorectal carcinoma cells. Pharmacological inhibition of Enox1 in endothelial cells inhibited repair of DNA double strand breaks, as measured by γH2AX and 53BP1 foci formation, as well as neutral comet assays...
October 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27786593/hypoxia-activated-cytotoxicity-of-benznidazole-against-clonogenic-tumor-cells
#13
Quhuan Li, Qun Lin, Zhong Yun
Solid tumors contain numerous regions with insufficient oxygen concentrations, a condition termed hypoxia. Tumor hypoxia is significantly associated with metastasis, refractory to conventional cancer therapies, and poor patient survival. Therefore, eradication of hypoxic tumor cells will likely have significant impact on the overall progression-free patient survival. This article reports a new discovery that Benznidazole, a bioreductive drug currently used to treat Chagas disease caused by the parasitic protozoan Trypanosoma cruzi, is activated by hypoxia and can kill clonogenic tumor cells especially those under severe hypoxic conditions (≤0...
October 27, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27752097/dna-damage-precedes-apoptosis-during-the-regression-of-the-interdigital-tissue-in-vertebrate-embryos
#14
Juan A Montero, Cristina Sanchez-Fernandez, Carlos I Lorda-Diez, Juan A Garcia-Porrero, Juan M Hurle
DNA damage independent of caspase activation accompanies programmed cell death in different vertebrate embryonic organs. We analyzed the significance of DNA damage during the regression of the interdigital tissue, which sculpts the digits in the embryonic limb. Interdigit remodeling involves oxidative stress, massive apoptosis and cell senescence. Phosphorylation of H2AX mediated by ATM precedes caspase dependent apoptosis and cell senescence during interdigit regression. The association of γH2AX with other downstream DNA repair factors, including MDC1, Rad50 and 53BP1 suggests a defensive response of cells against DNA damage...
October 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27716574/the-effect-of-delphinidin-on-the-mechanical-properties-of-keratinocytes-exposed-to-uvb-radiation
#15
Anna Sobiepanek, Małgorzata Milner-Krawczyk, Konstancja Bobecka-Wesołowska, Tomasz Kobiela
The usage of active compounds of dietary phytochemicals in prevention of UV-induced skin diseases is increasingly gaining attention in the development of skin care products. The purpose of this study was to measure the influence of delphinidin (as a botanical agent) on the cell mechanical properties evaluated by the atomic force microscopy (AFM) technique in the immortalized human keratinocyte cell line (HaCaT) exposed to UVB radiation. The cells were treated with various doses of UVB radiation with and without pre and post-treatment with selected concentrations of delphinidin...
September 29, 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/27716486/53bp1-goes-back-to-its-p53-roots
#16
Daniel Durocher, Laurence Pelletier
In this issue of Molecular Cell, Cuella-Martin et al. (2016) revisit the role of 53BP1 in p53-dependent responses and find that these functions are separable from its widely known function in DNA repair.
October 6, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27715493/phosphorylation-of-the-cajal-body-protein-wrap53%C3%AE-by-atm-promotes-its-involvement-in-the-dna-damage-response
#17
Christos Coucoravas, Soniya Dhanjal, Sofia Henriksson, Stefanie Böhm, Marianne Farnebo
The cellular response to DNA double-strand breaks is orchestrated by the protein kinase ATM, which phosphorylates key actors in the DNA repair network. WRAP53β is a multifunctional protein that controls trafficking of factors to Cajal bodies, telomeres and DNA double-strand breaks but what regulates the involvement of WRAP53β in these separate processes remains unclear. Here, we show that in response to various types of DNA damage, including IR and UV, WRAP53β is phosphorylated on serine residue 64 by ATM with a time-course that parallels its accumulation at DNA lesions...
October 7, 2016: RNA Biology
https://www.readbyqxmd.com/read/27692298/linking-genotoxicity-and-cytotoxicity-with-membrane-fluidity-a-comparative-study-in-ovarian-cancer-cell-lines-following-exposure-to-auranofin
#18
Deepu Oommen, Nicholas J F Dodd, Dennis Yiannakis, Rana Moyeed, Awadhesh N Jha
Auranofin, an organogold compound classified as an anti-rheumatic agent is under phase 2 clinical trials for re-purposing to treat recurrent epithelial ovarian cancer. We have reported earlier that Breast cancer 1, early onset (BRCA1) mutant ovarian cancer cells exhibit increased sensitivity to auranofin. BRCA1 is a DNA repair protein whose functional status is critical in the prognosis of ovarian cancer. Apart from DNA repair capability of cancer cells, membrane fluidity is also implicated in modulating resistance to chemotherapeutics...
October 2016: Mutation Research
https://www.readbyqxmd.com/read/27690219/mk-8776-a-novel-chk1-kinase-inhibitor-radiosensitizes-p53-defective-human-tumor-cells
#19
Kathleen A Bridges, Xingxing Chen, Huifeng Liu, Crosby Rock, Thomas A Buchholz, Stuart D Shumway, Heath D Skinner, Raymond E Meyn
Radiotherapy is commonly used to treat a variety of solid tumors but improvements in the therapeutic ratio are sorely needed. The aim of this study was to assess the Chk1 kinase inhibitor, MK-8776, for its ability to radiosensitize human tumor cells. Cells derived from NSCLC and HNSCC cancers were tested for radiosensitization by MK-8776. The ability of MK-8776 to abrogate the radiation-induced G2 block was determined using flow cytometry. Effects on repair of radiation-induced DNA double strand breaks (DSBs) were determined on the basis of rad51, γ-H2AX and 53BP1 foci...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27689875/the-role-of-53bp1-protein-in-homology-directed-dna-repair-things-get-a-bit-complicated
#20
Michal Malewicz
No abstract text is available yet for this article.
December 2016: Cell Death and Differentiation
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