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Parp1 dna

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https://www.readbyqxmd.com/read/28087741/14-3-3sigma-contributes-to-radioresistance-by-regulating-dna-repair-and-cell-cycle-via-parp1-and-chk2
#1
Yifan Chen, Zhaomin Li, Zizheng Dong, Jenny Beebe, Ke Yang, Liwu Fu, Jian-Ting Zhang
: 14-3-3sigma has been implicated in the development of chemo and radiation resistance and in poor prognosis of multiple human cancers. While it has been postulated that 14-3-3sigma contributes to these resistances via inhibiting apoptosis and arresting cells in G2/M phase of the cell cycle, the molecular basis of this regulation is currently unknown. In this study, we tested the hypothesis that 14-3-3sigma causes resistance to DNA-damaging treatments by enhancing DNA repair in cells arrested in G2/M phase following DNA-damaging treatments...
January 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28069995/atm-induces-macrod2-nuclear-export-upon-dna-damage
#2
Barbara Golia, Giuliana Katharina Moeller, Gytis Jankevicius, Andreas Schmidt, Anna Hegele, Julia Preißer, Mai Ly Tran, Axel Imhof, Gyula Timinszky
ADP-ribosylation is a dynamic post-translation modification that regulates the early phase of various DNA repair pathways by recruiting repair factors to chromatin. ADP-ribosylation levels are defined by the activities of specific transferases and hydrolases. However, except for the transferase PARP1/ARDT1 little is known about regulation of these enzymes. We found that MacroD2, a mono-ADP-ribosylhydrolase, is exported from the nucleus upon DNA damage, and that this nuclear export is induced by ATM activity...
January 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28042738/mir-520-promotes-dna-damage-induced-trophoblast-cell-apoptosis-by-targeting-parp1-in-recurrent-spontaneous-abortion-rsa
#3
Xiujuan Dong, Long Yang, Hui Wang
The establishment and maintenance of successful pregnancy mainly depends on trophoblast cells. Their dysfunction has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy. However, the underlying mechanisms of trophoblasts dysfunction remain unclear. DNA-damage-induced cell apoptosis has been reported to play a vital role in cell death. In this study, we identified a novel microRNA (miR-520) in RSA progression via regulating trophoblast cell apoptosis. Microarray analysis showed that miR-520 was highly expressed in villus of RSA patients...
December 31, 2016: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28039772/synthesis-crystal-structures-and-antitumor-activity-of-two-platinum-ii-complexes-with-methyl-hydrazinecarbodithioate-derivatives-of-indolin-2-one
#4
You-Shan Li, Bin Peng, Li Ma, Sheng-Li Cao, Lu-Lu Bai, Chao-Rui Yang, Chong-Qing Wan, Hao-Jie Yan, Pan-Pan Ding, Zhong-Feng Li, Ji Liao, Ying-Ying Meng, Hai-Long Wang, Jing Li, Xingzhi Xu
Two new platinum(II) complexes 7a and 7b with methyl hydrazinecarbodithioate derivatives of indolin-2-one have been prepared and characterized by single-crystal X-ray diffraction, NMR spectroscopy and mass spectrometry. Antiproliferative activity of the two complexes and their ligands 6a and 6b against HCT-116, MCF-7 and MDA-MB-231 cell lines was determined by the MTS assay. Complexes 7a and 7b exhibited stronger antiproliferative activity against three cell lines than compounds 6a and 6b (IC50, 1.89-5.60 versus 6...
December 26, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28034960/elevated-dna-oxidation-and-dna-repair-enzyme-expression-in-brain-white-matter-in-major-depressive-disorder
#5
Attila Szebeni, Katalin Szebeni, Timothy P DiPeri, Luke A Johnson, Craig A Stockmeier, Jessica D Crawford, Michelle J Chandley, Liza J Hernandez, Katherine C Burgess, Russell W Brown, Gregory A Ordway
BACKGROUND: Pathology of white matter in brains of patients with major depressive disorder (MDD) is well-documented, but the cellular and molecular basis of this pathology are poorly understood. METHODS: Levels of DNA oxidation and gene expression of DNA damage repair enzymes were measured in Brodmann area 10 (BA10) and/or amygdala (uncinate fasciculus) white matter tissue from brains of MDD (n=10) and psychiatrically normal control donors (n=13). DNA oxidation was also measured in BA10 white matter of schizophrenia donors (n=10) and in prefrontal cortical white matter from control rats (n=8) and rats with repeated stress-induced anhedonia (n=8)...
December 29, 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28034751/mln4924-suppresses-the-brca1-complex-and-synergizes-with-parp-inhibition-in-nsclc-cells
#6
Zong-Pei Guo, Ying-Chun Hu, Yu Xie, Feng Jin, Zhi-Quan Song, Xiao-Dan Liu, Teng Ma, Ping-Kun Zhou
Like ubiquitination, several studies have demonstrated that neddylation is implicated to be involved in the double strand break repair. BRCA1 is one of the key repair factors in the homologous recombination repair and may play a downstream role of the neddylation. BRCA1 is also a frequently mutated gene in cancers, which serve as the targets for PARP inhibitors. Here we further investigated the correlation between neddylation and BRCA1 complex using neddylation inhibitor MLN4924. MLN4924 efficiently inhibited the recruitment of components of BRCA1 complex to DNA damage sites...
December 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28010926/increased-methylation-of-repetitive-elements-and-dna-repair-genes-is-associated-with-higher-dna-oxidation-in-children-in-an-urbanized-industrial-environment
#7
Isabel Alvarado-Cruz, Marco Sánchez-Guerra, Leticia Hernández-Cadena, Andrea De Vizcaya-Ruiz, Violeta Mugica, Nadia Azenet Pelallo-Martínez, María de Jesús Solís-Heredia, Hyang-Min Byun, Andrea Baccarelli, Betzabet Quintanilla-Vega
DNA methylation in DNA repair genes participates in the DNA damage regulation. Particulate matter (PM), which has metals and polycyclic aromatic hydrocarbons (PAHs) adsorbed, among others has been linked to adverse health outcomes and may modify DNA methylation. To evaluate PM exposure impact on repetitive elements and gene-specific DNA methylation and DNA damage, we conducted a cross-sectional study in 150 schoolchildren (7-10 years old) from an urbanized, industrial area of the metropolitan area of Mexico City (MAMC), which frequently exhibits PM concentrations above safety standards...
January 2017: Mutation Research
https://www.readbyqxmd.com/read/28002403/xrcc1-mutation-is-associated-with-parp1-hyperactivation-and-cerebellar-ataxia
#8
Nicolas C Hoch, Hana Hanzlikova, Stuart L Rulten, Martine Tétreault, Emilia Komulainen, Limei Ju, Peter Hornyak, Zhihong Zeng, William Gittens, Stephanie A Rey, Kevin Staras, Grazia M S Mancini, Peter J McKinnon, Zhao-Qi Wang, Justin D Wagner, Grace Yoon, Keith W Caldecott
XRCC1 is a molecular scaffold protein that assembles multi-protein complexes involved in DNA single-strand break repair. Here we show that biallelic mutations in the human XRCC1 gene are associated with ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia. Cells from a patient with mutations in XRCC1 exhibited not only reduced rates of single-strand break repair but also elevated levels of protein ADP-ribosylation. This latter phenotype is recapitulated in a related syndrome caused by mutations in the XRCC1 partner protein PNKP and implicates hyperactivation of poly(ADP-ribose) polymerase/s as a cause of cerebellar ataxia...
January 5, 2017: Nature
https://www.readbyqxmd.com/read/27996159/persistent-phosphorylation-at-specific-h3-serine-residues-involved-in-chemical-carcinogen-induced-cell-transformation
#9
Xiaonian Zhu, Daochuan Li, Zhengbao Zhang, Wei Zhu, Wenxue Li, Jian Zhao, Xiumei Xing, Zhini He, Shan Wang, Fangping Wang, Lu Ma, Qing Bai, Xiaowen Zeng, Jie Li, Chen Gao, Yongmei Xiao, Qing Wang, Liping Chen, Wen Chen
Identification of aberrant histone H3 phosphorylation during chemical carcinogenesis will lead to a better understanding of the substantial roles of histone modifications in cancer development. To explore whether aberrant H3 phosphorylation contributes to chemical carcinogenesis, we examined the dynamic changes of H3 phosphorylation at various residues in chemical carcinogen-induced transformed human cells and human cancers. We found that histone H3 phosphorylation at Ser10 (p-H3S10) and Ser28 (p-H3S28) were up-regulated by 1...
December 20, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27995160/dataset-of-trans-resveratrol-on-diabetes-induced-abnormal-spermatogenesis-poly-adp-ribose-polymerase-1-parp1-expression-in-intra-testicular-blood-vessels-and-stage-dependent-expression-of-parp1-and-sirtuin-1-in-the-rat-testis
#10
Ala Abdelali, Maie Al-Bader, Narayana Kilarkaje
This article contains data related to the article "Effects of Trans-Resveratrol on hyperglycemia-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase signaling in rat testis" (A. Abdelali, M. Al-Bader, N. Kilarkaje, 2016) [1]. The data are related to Resveratrol on diabetes-induced changes in blood glucose levels, body weights of rats, sperm count and motility, expression of poly (ADP-ribose) polymerase-1 (PARP1) in Leydig cells and in intratesticular blood vessels, and stage-dependent expression of PARP1 and Sirtuin 1 (SirT1) in the rat testis...
February 2017: Data in Brief
https://www.readbyqxmd.com/read/27994596/cytoplasm-translocated-ku70-80-complex-sensing-of-hbv-dna-induces-hepatitis-associated-chemokine-secretion
#11
Young Li, Yang Wu, Xiaohu Zheng, Jingjing Cong, Yanyan Liu, Jiabin Li, Rui Sun, Zhigang G Tian, Haiming M Wei
Chronic hepatitis B virus (HBV) infection remains a serious disease, mainly due to its severe pathological consequences, which are difficult to cure using current therapies. When the immune system responds to hepatocytes experiencing rapid HBV replication, effector cells (such as HBV-specific CD8+ T cells, NK cells, NKT cells, and other subtypes of immune cells) infiltrate the liver and cause hepatitis. However, the precise recruitment of these cells remains unclear. In the present study, we found that the cytoplasm-translocated Ku70/80 complex in liver-derived cells sensed cytosolic HBV DNA and promoted hepatitis-associated chemokine secretion...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27965414/overlapping-roles-for-parp1-and-parp2-in-the-recruitment-of-endogenous-xrcc1-and-pnkp-into-oxidized-chromatin
#12
Hana Hanzlikova, William Gittens, Katerina Krejcikova, Zhihong Zeng, Keith W Caldecott
A critical step of DNA single-strand break repair is the rapid recruitment of the scaffold protein XRCC1 that interacts with, stabilizes and stimulates multiple enzymatic components of the repair process. XRCC1 recruitment is promoted by PARP1, an enzyme that is activated following DNA damage and synthesizes ADP-ribose polymers that XRCC1 binds directly. However, cells possess two other DNA strand break-induced PARP enzymes, PARP2 and PARP3, for which the roles are unclear. To address their involvement in the recruitment of endogenous XRCC1 into oxidized chromatin we have established 'isogenic' human diploid cells in which PARP1 and/or PARP2, or PARP3 are deleted...
December 13, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27960087/leveraging-an-nqo1-bioactivatable-drug-for-tumor-selective-use-of-poly-adp-ribose-polymerase-inhibitors
#13
Xiumei Huang, Edward A Motea, Zachary R Moore, Jun Yao, Ying Dong, Gaurab Chakrabarti, Jessica A Kilgore, Molly A Silvers, Praveen L Patidar, Agnieszka Cholka, Farjana Fattah, Yoonjeong Cha, Glenda G Anderson, Rebecca Kusko, Michael Peyton, Jingsheng Yan, Xian-Jin Xie, Venetia Sarode, Noelle S Williams, John D Minna, Muhammad Beg, David E Gerber, Erik A Bey, David A Boothman
Therapeutic drugs that block DNA repair, including poly(ADP-ribose) polymerase (PARP) inhibitors, fail due to lack of tumor-selectivity. When PARP inhibitors and β-lapachone are combined, synergistic antitumor activity results from sustained NAD(P)H levels that refuel NQO1-dependent futile redox drug recycling. Significant oxygen-consumption-rate/reactive oxygen species cause dramatic DNA lesion increases that are not repaired due to PARP inhibition. In NQO1(+) cancers, such as non-small-cell lung, pancreatic, and breast cancers, cell death mechanism switches from PARP1 hyperactivation-mediated programmed necrosis with β-lapachone monotherapy to synergistic tumor-selective, caspase-dependent apoptosis with PARP inhibitors and β-lapachone...
December 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27943678/cytotoxicity-of-tirapazamine-3-amino-1-2-4-benzotriazine-1-4-dioxide-induced-dna-damage-in-chicken-dt40-cells
#14
Takahito Moriwaki, Saki Okamoto, Hiroyuki Sasanuma, Hideko Nagasawa, Shunichi Takeda, Shin-Ichiro Masunaga, Keizo Tano
Tirapazamine (TPZ) is an anticancer drug with highly selective cytotoxicity toward hypoxic cells. TPZ is converted to a radical intermediate under hypoxic conditions, and this intermediate interacts with intracellular macromolecules, including DNA. TPZ has been reported to indirectly induce DNA double-strand breaks (DSBs) through the formation of various intermediate DNA lesions under hypoxic conditions. Although the topoisomerase II-DNA complex has been identified as one of these intermediates, other lesions have not yet been defined...
December 27, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27923837/the-nci-60-methylome-and-its-integration-into-cellminer
#15
William C Reinhold, Sudhir Varma, Margot Sunshine, Vinodh Rajapakse, Augustin Luna, Kurt W Kohn, Holly Stevenson, Yonghong Wang, Holger Heyn, Vanesa Nogales, Sebastian Moran, David J Goldstein, James H Doroshow, Paul S Meltzer, Manel Esteller, Yves Pommier
A unique resource for systems pharmacology and genomic studies is the NCI-60 cancer cell line panel, which provides data for the largest publicly available library of compounds with cytotoxic activity (~21,000 compounds), including 108 FDA-approved and 70 clinical trial drugs as well as genomic data, including whole-exome sequencing, gene and microRNA transcripts, DNA copy number, and protein levels. Here we provide the first readily usable genome-wide DNA methylation database for the NCI-60, including 485,577 probes from the Infinium HumanMethylation450k BeadChip array, which yielded DNA methylation signatures for 17,559 genes integrated into our open access CellMiner version 2...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27920426/crystal-structure-based-discovery-of-a-novel-synthesized-parp1-inhibitor-ol-1-with-apoptosis-inducing-mechanisms-in-triple-negative-breast-cancer
#16
Leilei Fu, Shuya Wang, Xuan Wang, Peiqi Wang, Yaxin Zheng, Dahong Yao, Mingrui Guo, Lan Zhang, Liang Ouyang
Poly (ADP-ribose) polymerase-1 (PARP1) is a highly conserved enzyme focused on the self-repair of cellular DNA damage. Until now, numbers of PARP inhibitors have been reported and used for breast cancer therapy in recent years, especially in TNBC. However, developing a new type PARP inhibitor with distinctive skeleton is alternatively promising strategy for TNBC therapy. In this study, based on co-crystallization studies and pharmacophore-docking-based virtual screening, we discovered a series of dihydrodibenzo[b,e]-oxepin compounds as PARP1 inhibitors...
December 2016: Scientific Reports
https://www.readbyqxmd.com/read/27908606/parp1-orchestrates-epigenetic-events-setting-up-chromatin-domains
#17
REVIEW
Fabio Ciccarone, Michele Zampieri, Paola Caiafa
Epigenetic events include reversible modifications of DNA and histone tails driving chromatin organization and thus transcription. The epigenetic regulation is a highly integrated process underlying the plasticity of the genomic information both in the context of complex physiological and pathological processes. The global regulatory aspects of epigenetic events are largely unknown. PARylation and PARP1 are recently emerging as multi-level regulatory effectors that modulate the topology of chromatin by orchestrating very different processes...
November 28, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27902462/the-synthetic-lethal-killing-of-rad54b-deficient-colorectal-cancer-cells-by-parp1-inhibition-is-enhanced-with-sod1-inhibition
#18
Erin N McAndrew, Chloe C Lepage, Kirk J McManus
Colorectal cancer (CRC) is a leading cause of cancer-related death throughout the world. Despite improved screening efforts, most CRCs are diagnosed at late stages when surgery alone is not curative. Moreover, the low 5-year survival rate (~8-13%) for those living with stage IV CRC highlights the need for better treatment options. Many current chemotherapeutic approaches are non-specific and associated with side effects due to their tendency to target both normal and cancer cells. To address this issue, synthetic lethal (SL) approaches are now being explored in cancer and are defined as the lethal combination of two independently viable mutations/deletions...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27890643/coordination-of-dna-single-strand-break-repair
#19
Rachel Abbotts, David M Wilson
The genetic material of all organisms is susceptible to modification. In some instances, these changes are programmed, such as the formation of DNA double strand breaks during meiotic recombination to generate gamete variety or class switch recombination to create antibody diversity. However, in most cases, genomic damage is potentially harmful to the health of the organism, contributing to disease and aging by promoting deleterious cellular outcomes. A proportion of DNA modifications are caused by exogenous agents, both physical (namely ultraviolet sunlight and ionizing radiation) and chemical (such as benzopyrene, alkylating agents, platinum compounds and psoralens), which can produce numerous forms of DNA damage, including a range of "simple" and helix-distorting base lesions, abasic sites, crosslinks and various types of phosphodiester strand breaks...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27866211/single-nucleotide-polymorphisms-of-genes-involved-in-repair-of-oxidative-dna-damage-and-the-risk-of-recurrent-depressive-disorder
#20
Piotr Czarny, Dominik Kwiatkowski, Monika Toma, Piotr Gałecki, Agata Orzechowska, Kinga Bobińska, Anna Bielecka-Kowalska, Janusz Szemraj, Michael Berk, George Anderson, Tomasz Śliwiński
BACKGROUND Depressive disorder, including recurrent type (rDD), is accompanied by increased oxidative stress and activation of inflammatory pathways, which may induce DNA damage. This thesis is supported by the presence of increased levels of DNA damage in depressed patients. Such DNA damage is repaired by the base excision repair (BER) pathway. BER efficiency may be influenced by polymorphisms in BER-related genes. Therefore, we genotyped nine single-nucleotide polymorphisms (SNPs) in six genes encoding BER proteins...
November 20, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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