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https://www.readbyqxmd.com/read/29121337/parp1-changes-from-three-dimensional-dna-damage-searching-to-one-dimensional-diffusion-after-auto-parylation-or-in-the-presence-of-ape1
#1
Lili Liu, Muwen Kong, Natalie R Gassman, Bret D Freudenthal, Rajendra Prasad, Stephanie Zhen, Simon C Watkins, Samuel H Wilson, Bennett Van Houten
PARP1-dependent poly-ADP-ribosylation (PARylation) participates in the repair of many forms of DNA damage. Here, we used atomic force microscopy (AFM) and single molecule fluorescence microscopy to examine the interactions of PARP1 with common DNA repair intermediates. AFM volume analysis indicates that PARP1 binds to DNA at nicks, abasic (AP) sites, and ends as a monomer. Single molecule DNA tightrope assays were used to follow the real-time dynamic behavior of PARP1 in the absence and presence of AP endonuclease (APE1) on AP DNA damage arrays...
November 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29055871/acute-telomerase-components-depletion-triggers-oxidative-stress-as-an-early-event-previous-to-telomeric-shortening
#2
José Santiago Ibáñez-Cabellos, Giselle Pérez-Machado, Marta Seco-Cervera, Ester Berenguer-Pascual, José Luis García-Giménez, Federico V Pallardó
Loss of function of dyskerin (DKC1), NOP10 and TIN2 are responsible for different inheritance patterns of Dyskeratosis congenita (DC; ORPHA1775). They are key components of telomerase (DKC1 and NOP10) and shelterin (TIN2), and play an important role in telomere homeostasis. They participate in several fundamental cellular processes by contributing to Dyskeratosis congenita through mechanisms that are not fully understood. Presence of oxidative stress was postulated to result from telomerase ablation. However, the resulting disturbed redox status can promote telomere attrition by generating a vicious circle, which promotes cellular senescence...
October 7, 2017: Redox Biology
https://www.readbyqxmd.com/read/29050247/rnai-mediated-knockdown-of-parp1-does-not-improve-the-development-of-female-cloned-mouse-embryos
#3
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...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029387/the-%C3%AE-nad-salvage-pathway-and-pkc-mediated-signaling-influence-localized-parp-1-activity-and-ctcf-poly-adp-ribosylation
#4
David J P Henderson, Jj L Miranda, Beverly M Emerson
Poly(ADP)ribosylation (PARylation) of the chromatin architectural protein CTCF is critical for CTCF-dependent regulation of chromatin boundary and insulator elements. Loss of CTCF PARylation results in epigenetic silencing of certain tumor suppressor genes through destabilization of nearby chromatin boundaries. We investigated the metabolic and mechanistic processes that regulate PARP-1-mediated CTCF PARylation in human cancer cell lines and discovered a key role for the expression and activity of β-NAD+ salvage enzymes, NAMPT and NMNAT-1...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28993228/kinase-independent-role-of-nuclear-ripk1-in-regulating-parthanatos-through-physical-interaction-with-parp1-upon-oxidative-stress
#5
Ki-Hong Jang, Taeik Jang, Eunji Son, Soonjin Choi, Eunhee Kim
Regulated necrosis occurs in various pathophysiological conditions under oxidative stress. Here, we report that receptor-interacting protein kinase 1 (RIPK1), a key player in one type of regulated necrosis (necroptosis), also participates in another type of poly (ADP-ribose) polymerase 1 (PARP1)-dependent regulated necrosis (parthanatos). Various biological signatures of parthanatos were significantly attenuated in Ripk1(-/-) mouse embryonic fibroblasts, including PARylation, nuclear translocation of apoptosis-inducing factor, and PARP1-dependent cell death under H2O2 exposure...
October 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28983606/parp%C3%A2-1-may-be-involved-in-hydroquinone%C3%A2-induced-apoptosis-by-poly-adp%C3%A2-ribosylation-of-zo%C3%A2-2
#6
Jiaxian Liu, Qian Yuan, Xiaoxuan Ling, Qiang Tan, Hairong Liang, Jialong Chen, Lianzai Lin, Yongmei Xiao, Wen Chen, Linhua Liu, Huanwen Tang
Hydroquinone (HQ), a major reactive metabolite of benzene, contributes to benzene‑induced leukemia. The molecular mechanisms that underlie this activity remain to be elucidated. Poly ADP‑ribosylation (PARylation) is a type of reversible posttranslational modification that is performed by enzymes in the PAR polymerase (PARP) family and mediates different biological processes, including apoptosis. Zona occludens 2 (ZO‑2) is a tight junction scaffold protein, which is involved in cell proliferation and apoptosis...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28977496/kinetics-of-poly-adp-ribosyl-ation-but-not-parp1-itself-determines-the-cell-fate-in-response-to-dna-damage-in-vitro-and-in-vivo
#7
Harald Schuhwerk, Christopher Bruhn, Kanstantsin Siniuk, Wookee Min, Suheda Erener, Paulius Grigaravicius, Annika Krüger, Elena Ferrari, Tabea Zubel, David Lazaro, Shamci Monajembashi, Kirstin Kiesow, Torsten Kroll, Alexander Bürkle, Aswin Mangerich, Michael Hottiger, Zhao-Qi Wang
One of the fastest cellular responses to genotoxic stress is the formation of poly(ADP-ribose) polymers (PAR) by poly(ADP-ribose)polymerase 1 (PARP1, or ARTD1). PARP1 and its enzymatic product PAR regulate diverse biological processes, such as DNA repair, chromatin remodeling, transcription and cell death. However, the inter-dependent function of the PARP1 protein and its enzymatic activity clouds the mechanism underlying the biological response. We generated a PARP1 knock-in mouse model carrying a point mutation in the catalytic domain of PARP1 (D993A), which impairs the kinetics of the PARP1 activity and the PAR chain complexity in vitro and in vivo, designated as hypo-PARylation...
August 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28925391/ezh2-contributes-to-the-response-to-parp-inhibitors-through-its-parp-mediated-poly-adp-ribosylation-in-breast-cancer
#8
H Yamaguchi, Y Du, K Nakai, M Ding, S-S Chang, J L Hsu, J Yao, Y Wei, L Nie, S Jiao, W-C Chang, C-H Chen, Y Yu, G N Hortobagyi, M-C Hung
Inhibitors against poly (ADP-ribose) polymerase (PARP) are promising targeted agents currently used to treat BRCA-mutant ovarian cancer and are in clinical trials for other cancer types, including BRCA-mutant breast cancer. To enhance the clinical response to PARP inhibitors (PARPis), understanding the mechanisms underlying PARPi sensitivity is urgently needed. Here, we show enhancer of zeste homolog 2 (EZH2), an enzyme that catalyzes H3 lysine trimethylation and associates with oncogenic function, contributes to PARPi sensitivity in breast cancer cells...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28910490/regulation-of-wnt-%C3%AE-catenin-signalling-by-tankyrase-dependent-poly-adp-ribosyl-ation-and-scaffolding
#9
REVIEW
Laura Mariotti, Katie Pollock, Sebastian Guettler
The Wnt/β-catenin signalling pathway is pivotal for stem cell function and the control of cellular differentiation, both during embryonic development and tissue homeostasis in adults. Its activity is carefully controlled through the concerted interactions of concentration-limited pathway components and a wide range of posttranslational modifications, including phosphorylation, ubiquitylation, sumoylation, poly(ADP-ribosyl)ation (PARylation) and acetylation. Regulation of Wnt/β-catenin signalling by PARylation was discovered relatively recently...
September 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28854736/the-role-of-poly-adp-ribosylation-in-the-first-wave-of-dna-damage-response
#10
Chao Liu, Aditi Vyas, Muzaffer A Kassab, Anup K Singh, Xiaochun Yu
Poly ADP-ribose polymerases (PARPs) catalyze massive protein poly ADP-ribosylation (PARylation) within seconds after the induction of DNA single- or double-strand breaks. PARylation occurs at or near the sites of DNA damage and promotes the recruitment of DNA repair factors via their poly ADP-ribose (PAR) binding domains. Several novel PAR-binding domains have been recently identified. Here, we summarize these and other recent findings suggesting that PARylation may be the critical event that mediates the first wave of the DNA damage response...
August 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28828398/poly-adp-ribose-polymerase-1-parp-1-induction-by-cocaine-is-post-transcriptionally-regulated-by-mir-125b
#11
Sabyasachi Dash, Muthukumar Balasubramaniam, Tanu Rana, Arthur Godino, Emily G Peck, Jeffery Shawn Goodwin, Fernando Villalta, Erin S Calipari, Eric J Nestler, Chandravanu Dash, Jui Pandhare
Cocaine exposure alters gene expression in the brain via methylation and acetylation of histones along with methylation of DNA. Recently, poly (ADP-ribose) polymerase-1 (PARP-1) catalyzed PARylation has been reported as an important regulator of cocaine-mediated gene expression. In this study, we report that the cellular microRNA "miR-125b" plays a key role for cocaine-induced PARP-1 expression. Acute and chronic cocaine exposure resulted in the downregulation of miR-125b concurrent with upregulation of PARP-1 in dopaminergic neuronal cells and nucleus accumbens (NAc) of mice but not in the medial prefrontal cortex (PFC) or ventral tegmental area (VTA)...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28767436/rnai-mediated-knockdown-of-parp1-does-not-improve-the-development-of-female-cloned-mouse-embryos
#12
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
#13
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...
September 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
#14
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
#15
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/28695503/cell-cycle-resolved-measurements-of-poly-adp-ribose-formation-and-dna-damage-signaling-by-quantitative-image-based-cytometry
#16
Jone Michelena, Matthias Altmeyer
Formation of poly(ADP-ribose) (PAR) marks intracellular stress signaling and is notably induced upon DNA damage. PAR polymerases (PARPs) catalyze PAR synthesis upon genotoxic stress and thereby recruit multiple proteins to damaged chromatin. PAR induction is transient and antagonized by the action of PAR glycohydrolase (PARG). Given that poly(ADP-ribosyl)ation (PARylation) is involved in genome integrity maintenance and other vital cellular functions, but also in light of the recent approval of PARP inhibitors for cancer treatments, reliable measurements of intracellular PAR formation have gained importance...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28695500/quantification-of-parp-activity-in-human-tissues-ex-vivo-assays-in-blood-cells-and-immunohistochemistry-in-human-biopsies
#17
Eszter M Horvath, Zsuzsanna K Zsengellér, Csaba Szabo
Poly(ADP-ribosyl)ation of proteins is a posttranslational modification mediated by poly(ADP-ribose) polymerases (PARPs) that use NAD(+) as substrate to form the negatively charged polymer of poly(ADP-ribose) (PAR). After DNA damage, PARP-1 is responsible for approximately 90% of the total cellular PARylation activity. Numerous studies showed activation of PARP-1 in various conditions associated with oxidative and nitrosative stress, such as ischemia-reperfusion injury, diabetes mellitus, and inflammation, and also proved the beneficial effects of PARP inhibitors...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28695499/quantitation-of-poly-adp-ribose-by-isotope-dilution-mass-spectrometry
#18
Tabea Zubel, Rita Martello, Alexander Bürkle, Aswin Mangerich
Poly(ADP-ribosyl)ation (PARylation), i.e., the formation of the nucleic acid-like biopolymer poly(ADP-ribose) (PAR), is an essential posttranslational modification carried out by poly(ADP-ribose) polymerases (PARPs). While PAR levels are low under physiological conditions, they can transiently increase more than 100-fold upon induction of genotoxic stress. The accurate quantitation of cellular PAR with high sensitivity is of critical importance to understand the role of PARylation in cellular physiology and pathophysiology and to determine the pharmacodynamic efficiencies of clinically relevant PARP inhibitors, which represent a novel class of promising chemotherapeutics...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28608282/poly-adp-ribosylated-proteins-in-mononuclear-cells-from-patients-with-type-2-diabetes-identified-by-proteomic-studies
#19
Alessandra Giorgi, Italo Tempera, Giorgia Napoletani, Diego Drovandi, Cinzia Potestà, Sara Martire, Elisabetta Mandosi, Tiziana Filardi, M Eugenia Schininà, Susanna Morano, Maria d'Erme, Bruno Maras
AIMS: In diabetes, hyperglycemia increases reactive oxygen species that induce DNA damage and poly(ADP-ribose)polymerase activation. The aim of this study is to characterize the proteomic profile and the role of poly(ADP-ribosylation) in patients with type 2 diabetes. METHODS: A proteomic platform based on 2DE and MALDI-ToF spectrometry was applied to peripheral blood mononuclear cells obtained from two different cohorts in which diabetic (n = 14) and normoglycemic patients (n = 11) were enrolled...
June 12, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28560323/ctcf-facilitates-dna-double-strand-break-repair-by-enhancing-homologous-recombination-repair
#20
Khalid Hilmi, Maïka Jangal, Maud Marques, Tiejun Zhao, Amine Saad, Chenxi Zhang, Vincent M Luo, Alasdair Syme, Carlis Rejon, Zhenbao Yu, Asiev Krum, Marc R Fabian, Stéphane Richard, Moulay Alaoui-Jamali, Alexander Orthwein, Luke McCaffrey, Michael Witcher
The repair of DNA double-strand breaks (DSBs) is mediated via two major pathways, nonhomologous end joining (NHEJ) and homologous recombination (HR) repair. DSB repair is vital for cell survival, genome stability, and tumor suppression. In contrast to NHEJ, HR relies on extensive homology and templated DNA synthesis to restore the sequence surrounding the break site. We report a new role for the multifunctional protein CCCTC-binding factor (CTCF) in facilitating HR-mediated DSB repair. CTCF is recruited to DSB through its zinc finger domain independently of poly(ADP-ribose) polymers, known as PARylation, catalyzed by poly(ADP-ribose) polymerase 1 (PARP-1)...
May 2017: Science Advances
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