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PARP1 parylation

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https://www.readbyqxmd.com/read/28767436/rnai-mediated-knockdown-of-parp1-does-not-improve-the-development-of-female-cloned-mouse-embryos
#1
Guang-Yu Bai, Si-Hang Song, Rui-Zhen Sun, Zi-Hui Zhang, Jingyu Li, Zhen-Dong Wang, Zhong-Hua Liu, Lei Lei
Somatic cell nuclear transfer is an important technique for life science research, but its efficiency is still extremely low, and most genes that are important during early development, such as X chromosome-linked genes, are not appropriately expressed during this process. Poly (ADP-ribose) polymerase (PARP) is an enzyme that transfers ADP ribose clusters to target proteins. PARP family members such as PARP1 participate in cellular signalling pathways through poly (ADP-ribosylation) (PARylation), which ultimately promotes changes in chromatin structure, gene expression, and the localization and activity of proteins that mediate signalling responses...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28759004/a-common-intronic-variant-of-parp1-confers-melanoma-risk-and-mediates-melanocyte-growth-via-regulation-of-mitf
#2
Jiyeon Choi, Mai Xu, Matthew M Makowski, Tongwu Zhang, Matthew H Law, Michael A Kovacs, Anton Granzhan, Wendy J Kim, Hemang Parikh, Michael Gartside, Jeffrey M Trent, Marie-Paule Teulade-Fichou, Mark M Iles, Julia A Newton-Bishop, D Timothy Bishop, Stuart MacGregor, Nicholas K Hayward, Michiel Vermeulen, Kevin M Brown
Previous genome-wide association studies have identified a melanoma-associated locus at 1q42.1 that encompasses a ∼100-kb region spanning the PARP1 gene. Expression quantitative trait locus (eQTL) analysis in multiple cell types of the melanocytic lineage consistently demonstrated that the 1q42.1 melanoma risk allele (rs3219090[G]) is correlated with higher PARP1 levels. In silico fine-mapping and functional validation identified a common intronic indel, rs144361550 (-/GGGCCC; r(2) = 0.947 with rs3219090), as displaying allele-specific transcriptional activity...
July 31, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28740101/p38-mapk-signaling-and-phosphorylations-in-the-brct1-domain-regulate-xrcc1-recruitment-to-sites-of-dna-damage
#3
Mirta Mittelstedt Leal de Sousa, Karine Øian Bjørås, Audun Hanssen-Bauer, Karin Solvang-Garten, Marit Otterlei
XRCC1 is a scaffold protein involved in base excision repair and single strand break repair. It is a phosphoprotein that contains more than 45 phosphorylation sites, however only a few of these have been characterized and connected to specific kinases and functions. Mitogen activated protein kinases (MAPK) are mediators of cellular stress responses, and here we demonstrate that p38 MAPK signaling is involved in phosphorylation of XRCC1 and regulation of recruitment to oxidative stress. Inhibition of p38 MAPK caused a marked pI shift of XRCC1 towards a less phosphorylated state...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28695510/poly-adp-ribose-dependent-chromatin-remodeling-in-dna-repair
#4
Théo Lebeaupin, Rebecca Smith, Sébastien Huet, Gyula Timinszky
The tightly packed and dynamic structure of chromatin can undergo major reorganization in response to endogenous or exogenous stimuli, such as the regulation of transcription or the cell cycle, or following DNA damage. A fast and local chromatin decondensation is observed upon DNA damage induced by laser micro-irradiation. This decondensation is under the control of poly(ADP-ribosyl)ation (PARylation) by PARP1, one of the first proteins recruited at the DNA damage sites. This chapter provides a step-by-step guide to perform and analyze chromatin decondensation upon DNA damage induction...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28510338/therapeutic-targeting-of-poly-adp-ribose-polymerase-1-in-cancer-current-developments-therapeutic-strategies-and-future-opportunities
#5
REVIEW
Jyotika Rajawat, Nidhi Shukla, Durga Prasad Mishra
Poly(ADP-ribose) polymerase-1 (PARP1) is key protein involved in numerous cellular processes including DNA repair, replication, and transcription. PARP interacts directly, indirectly, or via PARylation with various oncogenic proteins and regulates several transcription factors, thereby modulating carcinogenesis. Therapeutic inhibition of PARP is therefore perceived as a promising anticancer strategy, and a number of PARP inhibitors (PARPi) are in different stages of clinical evaluation. PARPi inhibit the DNA repair pathway and thus form the concept of synthetic lethality in cancer therapeutics...
May 16, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28442756/crystal-structure-based-discovery-of-a-novel-synthesized-parp1-inhibitor-ol-1-with-apoptosis-inducing-mechanisms-in-triple-negative-breast-cancer
#6
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 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28302504/mitochondrial-nudix-hydrolases-a-metabolic-link-between-nad-catabolism-gtp-and-mitochondrial-dynamics
#7
Aaron Long, Nina Klimova, Tibor Kristian
NAD(+) catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD(+) catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Additionally, several potential targets in mitochondrial dysfunction and fragmentation are discussed, including the roles of mitochondrial poly(ADP-ribose) polymerase 1(mtPARP1), AMPK, AMP, and intra-mitochondrial GTP metabolism...
March 14, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28272405/parp1-promotes-gene-expression-at-the-post-transcriptiona-level-by-modulating-the-rna-binding-protein-hur
#8
Yueshuang Ke, Yanlong Han, Xiaolan Guo, Jitao Wen, Ke Wang, Xue Jiang, Xue Tian, Xueqing Ba, Istvan Boldogh, Xianlu Zeng
Poly(ADP-ribosyl)ation (PARylation) is mainly catalysed by poly-ADP-ribose polymerase 1 (PARP1), whose role in gene transcription modulation has been well established. Here we show that, in response to LPS exposure, PARP1 interacts with the adenylateuridylate-rich element-binding protein embryonic lethal abnormal vision-like 1 (Elavl1)/human antigen R (HuR), resulting in its PARylation, primarily at site D226. PARP inhibition and the D226 mutation impair HuR's PARylation, nucleocytoplasmic shuttling and mRNA binding...
March 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28257697/serious-surprises-for-adp-ribosylation-specificity-hpf1-switches-parp1-specificity-to-ser-residues
#9
Anthony K L Leung
In this issue of Molecular Cell, Bonfiglio et al. (2017) demonstrate that histone PARylation factor 1 (HPF1) is required for PARP1 to attach ADP-ribose groups onto the hydroxyl oxygen of the Ser residues of target substrates, including both PARP1 itself and histones. Here, mechanisms and implications of this unexpected, O-linked ADP-ribosylation are speculated on.
March 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28249904/nr1d1-recruitment-to-sites-of-dna-damage-inhibits-repair-and-is-associated-with-chemosensitivity-of-breast-cancer
#10
Na-Lee Ka, Tae-Young Na, Hyelin Na, Min-Ho Lee, Han-Su Park, Sewon Hwang, Il Yong Kim, Je Kyung Seong, Mi-Ock Lee
DNA repair capacity is critical for survival of cancer cells upon therapeutic DNA damage and thus is an important determinant of susceptibility to chemotherapy in cancer patients. In this study, we identified a novel function of nuclear receptor NR1D1 in DNA repair, which enhanced chemosensitivity in breast cancer cells. NR1D1 inhibited both nonhomologous end joining and homologous recombination double-strand breaks repair, and delayed the clearance of γH2AX DNA repair foci that formed after treatment of doxorubicin...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28032120/inhibition-of-poly-adp-ribosylation-fails-to-increase-axonal-regeneration-or-improve-functional-recovery-after-adult-mammalian-cns-injury
#11
Xingxing Wang, Yuichi Sekine, Alexandra B Byrne, William B J Cafferty, Marc Hammarlund, Stephen M Strittmatter
After traumatic damage of the brain or spinal cord, many surviving neurons are disconnected, and recovery of function is limited by poor axon regeneration. Recent data have suggested that poly ADP-ribosylation plays a role in limiting axonal regrowth such that inhibition of poly (ADP-ribose) polymerase (PARP) may have therapeutic efficacy for neurological recovery after trauma. Here, we tested systemic administration of the PARP inhibitor, veliparib, and showed effective suppression of PARylation in the mouse CNS...
November 2016: ENeuro
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
#12
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
#13
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...
March 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27694308/analyzing-structure-function-relationships-of-artificial-and-cancer-associated-parp1-variants-by-reconstituting-talen-generated-hela-parp1-knock-out-cells
#14
Lisa Rank, Sebastian Veith, Eva C Gwosch, Janine Demgenski, Magdalena Ganz, Marjolijn C Jongmans, Christopher Vogel, Arthur Fischbach, Stefanie Buerger, Jan M F Fischer, Tabea Zubel, Anna Stier, Christina Renner, Michael Schmalz, Sascha Beneke, Marcus Groettrup, Roland P Kuiper, Alexander Bürkle, Elisa Ferrando-May, Aswin Mangerich
Genotoxic stress activates PARP1, resulting in the post-translational modification of proteins with poly(ADP-ribose) (PAR). We genetically deleted PARP1 in one of the most widely used human cell systems, i.e. HeLa cells, via TALEN-mediated gene targeting. After comprehensive characterization of these cells during genotoxic stress, we analyzed structure-function relationships of PARP1 by reconstituting PARP1 KO cells with a series of PARP1 variants. Firstly, we verified that the PARP1\E988K mutant exhibits mono-ADP-ribosylation activity and we demonstrate that the PARP1\L713F mutant is constitutively active in cells...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27686254/the-poly-adp-ribosyl-ation-of-foxo3-mediated-by-parp1-participates-in-isoproterenol-induced-cardiac-hypertrophy
#15
Jing Lu, Renwei Zhang, Huiqi Hong, Zuolong Yang, Duanping Sun, Shuya Sun, Xiaolei Guo, Jiantao Ye, Zhuoming Li, Peiqing Liu
The Forkhead box-containing protein, O subfamily 3 (FoxO3) transcription factor negatively regulates myocardial hypertrophy, and its transcriptional activity is finely conditioned by diverse posttranslational modifications, such as phosphorylation, acetylation, ubiquitination, methylation and glycosylation. Here, we introduce a novel modification of the FoxO3 protein in cardiomyocytes: poly(ADP-ribosyl)ation (PARylation) mediated by poly(ADP-ribose) polymerase-1 (PARP1). This process catalyzes the NAD(+)-dependent synthesis of polymers of ADP-ribose (PAR) and their subsequent attachment to target proteins by PARPs...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27670719/expanding-functions-of-adp-ribosylation-in-the-maintenance-of-genome-integrity
#16
REVIEW
K Martin-Hernandez, J-M Rodriguez-Vargas, V Schreiber, F Dantzer
Cell response to genotoxic stress requires a complex network of sensors and effectors from numerous signaling and repair pathways, among them the nuclear poly(ADP-ribose) polymerase 1 (PARP1) plays a central role. PARP1 is catalytically activated in the setting of DNA breaks. It uses NAD(+) as a donor and catalyses the synthesis and subsequent covalent attachment of branched ADP-ribose polymers onto itself and various acceptor proteins to promote repair. Its inhibition is now considered as an efficient therapeutic strategy to potentiate the cytotoxic effect of chemotherapy and radiation or to exploit synthetic lethality in tumours with defective homologous recombination mediated repair...
March 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27668604/-poly-adp-ribose-polymerase-1-as-a-key-regulator-of-dna-repair
#17
S N Khodyreva, O I Lavrik
Poly(ADP-ribosyl)ation (PARylation) of proteins is one of the immediate cell responses to DNA damage and is catalyzed by poly(ADP-ribose) polymerases (PARPs). When bound to damaged DNA, some members of the PARP family are activated and use NAD^(+) as a source of ADP to catalyze synthesis of poly(ADP-ribose) (PAR) covalently attached to a target protein. PAR synthesis is considered as a mechanism that provides a local signal of DNA damage and modulates protein functions in response to genotoxic agents. PARP1 is the best-studied protein of the PARP family and is widely known аs a regulator of repair of damaged bases and single-strand nicks...
July 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27664469/parping-for-balance-in-the-homeostasis-of-poly-adp-ribosyl-ation
#18
REVIEW
Harald Schuhwerk, Reham Atteya, Kanstantsin Siniuk, Zhao-Qi Wang
Despite more than 50 years of research, the vast majority of the biology of poly(ADP-ribosyl)ation (PARylation) still remains a gross mystery. Originally described to be a part of the DNA repair machinery, poly(ADP-ribose) (PAR) is synthesized immediately by poly(ADP-ribose) polymerases (PARPs, also known as ARTDs) upon DNA damage and then rapidly removed by degrading enzymes. PAR provides a delicate and spatiotemporal interaction scaffold for numerous target proteins. Thus, the multifaceted PARylation system, consisting of PAR itself and its synthesizers and erasers, plays diverse roles in the DNA damage response (DDR), in DNA repair, transcription, replication, chromatin remodelling, metabolism and cell death...
March 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27466387/poly-adp-ribose-polymers-regulate-dna-topoisomerase-i-top1-nuclear-dynamics-and-camptothecin-sensitivity-in-living-cells
#19
Subhendu K Das, Ishita Rehman, Arijit Ghosh, Souvik Sengupta, Papiya Majumdar, Biman Jana, Benu Brata Das
Topoisomerase 1 (Top1) is essential for removing the DNA supercoiling generated during replication and transcription. Anticancer drugs like camptothecin (CPT) and its clinical derivatives exert their cytotoxicity by reversibly trapping Top1 in covalent complexes on the DNA (Top1cc). Poly(ADP-ribose) polymerase (PARP) catalyses the addition of ADP-ribose polymers (PAR) onto itself and Top1. PARP inhibitors enhance the cytotoxicity of CPT in the clinical trials. However, the molecular mechanism by which PARylation regulates Top1 nuclear dynamics is not fully understood...
September 30, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27462443/involvement-of-parp1-in-the-regulation-of-alternative-splicing
#20
Elena Matveeva, John Maiorano, Qingyang Zhang, Abdallah M Eteleeb, Paolo Convertini, Jing Chen, Vittoria Infantino, Stefan Stamm, Jiping Wang, Eric C Rouchka, Yvonne N Fondufe-Mittendorf
Specialized chromatin structures such as nucleosomes with specific histone modifications decorate exons in eukaryotic genomes, suggesting a functional connection between chromatin organization and the regulation of pre-mRNA splicing. Through profiling the functional location of Poly (ADP) ribose polymerase, we observed that it is associated with the nucleosomes at exon/intron boundaries of specific genes, suggestive of a role for this enzyme in alternative splicing. Poly (ADP) ribose polymerase has previously been implicated in the PARylation of splicing factors as well as regulation of the histone modification H3K4me3, a mark critical for co-transcriptional splicing...
2016: Cell Discovery
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