In Vivo Level of Poly(ADP-ribose)

PolyADP-ribosylation is a post-translational modification that plays key roles in cellular physiological functions and DNA damage responses. PolyADP-ribosylation is finely and dynamically regulated by various enzymes and factors involved in the synthesis and degradation of poly(ADP-ribose) (PAR). To better understand the function of polyADP-ribosylation, it is necessary to quantify and monitor the change of the in vivo level of PAR, the product of polyADP-ribosylation, which is rapidly turning over and kept in quite low level in cells or in organs. Recent developments of potent inhibitors of polyADP-ribosylation is expected to kill BRCA1 / 2 -mutated breast cancer cells and ovarian cancer cells (synthetic lethality). To know the efficacy of these inhibitors in vivo, it is necessary to develop highly sensitive and reproducible methods to know PAR levels within cells or organs. However there have been several difficulties in measuring the physiologically low level of PAR without artefacts. Our experiments recently clarified that the method of sample preparation is very important in addition to the sensitivity and specificity. From reviewing the literature, including ours, we would like to emphasize the importance of the procedures of sample preparation for the assay, in addition to the sensitivity by comparing the reported PAR levels in vivo.

[1]  S. Snyder,et al.  Opportunities for the repurposing of PARP inhibitors for the therapy of non‐oncological diseases , 2018, British journal of pharmacology.

[2]  M. Masutani,et al.  Poly(ADP-ribosyl)ation in carcinogenesis. , 2013, Molecular aspects of medicine.

[3]  M. Smulson,et al.  Release of template restriction for DNA synthesis by poly ADP(ribose) polymerase during the HeLa cell cycle. , 1975, Experimental cell research.

[4]  M. Malanga,et al.  Poly(ADP-ribose) quantification at the femtomole level in mammalian cells. , 1995, Analytical biochemistry.

[5]  J. Moss,et al.  Identification and Characterization of a Mammalian 39-kDa Poly(ADP-ribose) Glycohydrolase* , 2006, Journal of Biological Chemistry.

[6]  J. Hoflack,et al.  Methods for biochemical study of poly(ADP-ribose) metabolism in vitro and in vivo. , 1995, Analytical biochemistry.

[7]  Y. Nishizuka,et al.  Studies on the polymer of adenosine diphosphate ribose. I. Enzymic formation from nicotinamide adenine dinuclotide in mammalian nuclei. , 1967, The Journal of biological chemistry.

[8]  V. Dawson,et al.  Role of poly(ADP-ribose) synthetase in inflammation and ischaemia-reperfusion. , 1998, Trends in pharmacological sciences.

[9]  W. Kraus,et al.  PARPs and ADP-Ribosylation: 50 Years … and Counting. , 2015, Molecular cell.

[10]  F. Althaus,et al.  ADP-ribosylation of proteins. Enzymology and biological significance. , 2012, Molecular biology, biochemistry, and biophysics.

[11]  T. Sugimura,et al.  Inhibitors of poly(adenosine diphosphate ribose) polymerase induce sister chromatid exchanges. , 1980, Biochemical and biophysical research communications.

[12]  W. Kraus.  Transcriptional control by PARP-1: chromatin modulation, enhancer-binding, coregulation, and insulation. , 2008, Current opinion in cell biology.

[13]  A. Bürkle,et al.  Quantification of cellular poly(ADP-ribosyl)ation by stable isotope dilution mass spectrometry reveals tissue- and drug-dependent stress response dynamics. , 2013, ACS chemical biology.

[14]  P. Mandel,et al.  Poly(ADP‐ribose) polymerase auto‐modification and interaction with DNA: electron microscopic visualization. , 1983, The EMBO journal.

[15]  I. Ahel,et al.  The recognition and removal of cellular poly(ADP‐ribose) signals , 2013, The FEBS journal.

[16]  S. Steinberg,et al.  Randomized phase II trial of cyclophosphamide and the oral poly (ADP-ribose) polymerase inhibitor veliparib in patients with recurrent, advanced triple-negative breast cancer , 2016, Investigational New Drugs.

[17]  Mitsuko Masutani,et al.  PolyADP‐ribosylation and cancer , 2007, Cancer science.

[18]  David R Goodlett,et al.  Mapping PARP-1 auto-ADP-ribosylation sites by liquid chromatography-tandem mass spectrometry. , 2013, Journal of proteome research.

[19]  O. Hayaishi,et al.  ADP-ribosylation of histone H2B. Identification of glutamic acid residue 2 as the modification site. , 1980, The Journal of biological chemistry.

[20]  T. Sugimura,et al.  Structure of poly(adenosine diphosphate ribose): identification of 2'-[1''-ribosyl-2''-(or 3''-)(1'''-ribosyl)]adenosine-5',5'',5'''-tris(phosphate) as a branch linkage. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[21]  N. Curtin,et al.  Therapeutic applications of PARP inhibitors: anticancer therapy and beyond. , 2013, Molecular aspects of medicine.

[22]  P. Adamietz,et al.  Protein-bound polymeric and monomeric ADP-ribose residues in hepatic tissues. Comparative analyses using a new procedure for the quantification of poly(ADP-ribose). , 2005, European journal of biochemistry.

[23]  M. Mage,et al.  Changes in poly(adenosine diphosphate-ribose) and poly(adenosine diphosphate-ribose) polymerase in synchronous HeLa cells. , 1976, Biochemistry.

[24]  F. Althaus,et al.  Noncovalent interactions of poly(adenosine diphosphate ribose) with histones. , 1992, Biochemistry.

[25]  Mo Li,et al.  Function of BRCA1 in the DNA damage response is mediated by ADP-ribosylation. , 2013, Cancer cell.

[26]  S. Wattler,et al.  Failure to degrade poly(ADP-ribose) causes increased sensitivity to cytotoxicity and early embryonic lethality. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Larry Rubinstein,et al.  A Phase I Study of Veliparib in Combination with Metronomic Cyclophosphamide in Adults with Refractory Solid Tumors and Lymphomas , 2012, Clinical Cancer Research.

[28]  T. Sugimura,et al.  Poly(adenosine diphosphate ribose). , 1973, Progress in nucleic acid research and molecular biology.

[29]  T. Sugimura,et al.  Monoclonal antibodies to poly(adenosine diphosphate ribose) recognize different structures. , 1984, Biochemistry.

[30]  M. Inghram.  Stable Isotope Dilution as an Analytical Tool , 1954 .

[31]  P. Chambon,et al.  On the formation of a novel adenylic compound by enzymatic extracts of liver nuclei , 1966 .

[32]  L. Galluzzi,et al.  Cisplatin resistance associated with PARP hyperactivation. , 2013, Cancer research.

[33]  H. Ohgushi,et al.  Enzyme-bound early product of purified poly(ADP-ribose) polymerase. , 1977, Biochemical and biophysical research communications.

[34]  A. Leung,et al.  The Promise of Proteomics for the Study of ADP-Ribosylation , 2015, Molecular Cell.

[35]  J. Moss,et al.  Effect of mild temperature shift on poly(ADP-ribose) and γH2AX levels in cultured cells. , 2016, Biochemical and biophysical research communications.

[36]  J. Smith,et al.  Identification of poly (ADP-ribose) covalently bound to histone F1 in vivo. , 1973, Biochemical and biophysical research communications.

[37]  C. Simbulan-Rosenthal,et al.  Purification and characterization of poly(ADP-ribosyl)ated DNA replication/repair complexes. , 2011, Methods in molecular biology.

[38]  Dr. Felix R. Althaus,et al.  ADP-Ribosylation of Proteins , 1987, Molecular Biology Biochemistry and Biophysics.

[39]  B. Durkacz,et al.  (ADP-ribose)n participates in DNA excision repair , 1980, Nature.

[40]  T. Dawson,et al.  Poly(ADP-Ribose) (PAR) Binding to Apoptosis-Inducing Factor Is Critical for PAR Polymerase-1–Dependent Cell Death (Parthanatos) , 2011, Science Signaling.

[41]  Claus Scheidereit,et al.  A nuclear poly(ADP-ribose)-dependent signalosome confers DNA damage-induced IkappaB kinase activation. , 2009, Molecular cell.

[42]  T. Sugimura,et al.  Natural occurence of a biopolymer, poly (adenosine diphosphate ribose). , 1977, Nucleic acids research.

[43]  M. Malanga,et al.  Noncovalent protein interaction with poly(ADP-ribose). , 2011, Methods in molecular biology.

[44]  A. Spradling,et al.  Chromatin Loosening by Poly(ADP)-Ribose Polymerase (PARP) at Drosophila Puff Loci , 2003, Science.

[45]  Z. Yao,et al.  DNA-independent PARP-1 activation by phosphorylated ERK2 increases Elk1 activity: a link to histone acetylation. , 2007, Molecular cell.

[46]  A. Tulin,et al.  Charon Mediates Immune Deficiency–Driven PARP-1–Dependent Immune Responses in Drosophila , 2016, The Journal of Immunology.

[47]  H. Kagamiyama,et al.  ADP-ribosylation of histone H1. Identification of glutamic acid residues 2, 14, and the COOH-terminal lysine residue as modification sites. , 1980, The Journal of biological chemistry.

[48]  P. Chambon,et al.  Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[49]  I. Matic,et al.  Deficiency of terminal ADP‐ribose protein glycohydrolase TARG1/C6orf130 in neurodegenerative disease , 2013, The EMBO journal.

[50]  H. Naegeli,et al.  Histone shuttling by poly ADP-ribosylation , 1992, Molecular and Cellular Biochemistry.

[51]  S. Hanai,et al.  Loss of poly(ADP-ribose) glycohydrolase causes progressive neurodegeneration in Drosophila melanogaster , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[52]  P. Poltronieri,et al.  Roles of Nicotinamide Adenine Dinucleotide (NAD+) in Biological Systems , 2018 .

[53]  I. Matic,et al.  Specificity of reversible ADP-ribosylation and regulation of cellular processes , 2018, Critical reviews in biochemistry and molecular biology.

[54]  I. Ahel,et al.  Structures and Mechanisms of Enzymes Employed in the Synthesis and Degradation of PARP-Dependent Protein ADP-Ribosylation. , 2015, Molecular cell.

[55]  I. Ahel,et al.  Molecular Insights into Poly(ADP-ribose) Recognition and Processing , 2012, Biomolecules.

[56]  K. Nakanishi,et al.  ADP-ribosyl protein lyase. Purification, properties, and identification of the product. , 1984, The Journal of biological chemistry.

[57]  S. Narumiya,et al.  Poly ADP-ribose glycohydrolase from rat liver nuclei, a novel enzyme degrading the polymer. , 1972, Biochemical and biophysical research communications.

[58]  金居 正幸.  Involvement of poly(ADP-ribose) polymerase 1 and poly(ADP-ribosyl)ation in regulation of centrosome function , 2004 .

[59]  T. Sugimura,et al.  Size and shape of poly(ADP-ribose): examination by gel filtration, gel electrophoresis and electron microscopy. , 1983, Biochemical and biophysical research communications.

[60]  Bernhard Lüscher,et al.  Toward a unified nomenclature for mammalian ADP-ribosyltransferases. , 2010, Trends in biochemical sciences.

[61]  T. Sugimura,et al.  Induction of sister chromatid exchanges by nicotinamide in Chinese hamster lung fibroblasts and human lymphoblastoid cells. , 1979, Biochemical and biophysical research communications.

[62]  Joel Moss,et al.  An enzyme-linked immunosorbent assay-based system for determining the physiological level of poly(ADP-ribose) in cultured cells. , 2016, Analytical biochemistry.

[63]  T. Lange,et al.  Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. , 1998, Science.

[64]  T. Sugimura,et al.  Naturally-occurring antibodies to poly(ADP-ribose) in patients with systemic lupus erythematosus , 1977, Nature.

[65]  J. Pleschke,et al.  Poly(ADP-ribose) Binds to Specific Domains in DNA Damage Checkpoint Proteins* , 2000, The Journal of Biological Chemistry.

[66]  M. Malanga,et al.  The role of poly(ADP-ribose) in the DNA damage signaling network. , 2005, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[67]  Thomas Helleday,et al.  Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase , 2007, Nature.

[68]  T. Ochiya,et al.  Poly(ADP-ribose) polymerase gene disruption conferred mice resistant to streptozotocin-induced diabetes. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[69]  P. Mandel,et al.  Correlation between endogenous nucleosomal hyper(ADP‐ribosyl)ation of histone H1 and the induction of chromatin relaxation. , 1983, The EMBO journal.

[70]  T. Sugimura,et al.  Splitting of the ribose-ribose linkage of poly(adenosine diphosphate-robose) by a calf thymus extract. , 1971, The Journal of biological chemistry.

[71]  L. Rubinstein,et al.  Modeling Pharmacodynamic Response to the Poly(ADP-Ribose) Polymerase Inhibitor ABT-888 in Human Peripheral Blood Mononuclear Cells , 2011, PloS one.

[72]  R. Mangano,et al.  Phase 2 multicentre trial investigating intermittent and continuous dosing schedules of the poly(ADP-ribose) polymerase inhibitor rucaparib in germline BRCA mutation carriers with advanced ovarian and breast cancer , 2016, British Journal of Cancer.

[73]  R. Bredehorst,et al.  Quantitative determination of poly(adenosine diphosphate ribose) in different hepatic tissues by an isotope dilution procedure. , 1976, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[74]  Martin Zacharias,et al.  A family of macrodomain proteins reverses cellular mono-ADP-ribosylation , 2013, Nature Structural &Molecular Biology.

[75]  Guy G. Poirier,et al.  Proteome-wide identification of poly(ADP-ribose) binding proteins and poly(ADP-ribose)-associated protein complexes , 2008, Nucleic acids research.

[76]  E. Jacobson,et al.  Poly(ADP-ribose) has a branched structure in vivo. , 1982, The Journal of biological chemistry.

[77]  James E. Evans,et al.  ART2, a T Cell Surface Mono-ADP-ribosyltransferase, Generates Extracellular Poly(ADP-ribose)* , 2006, Journal of Biological Chemistry.

[78]  E. Jacobson,et al.  Poly(ADP-ribose) metabolism in ultraviolet irradiated human fibroblasts. , 1983, The Journal of biological chemistry.

[79]  M. Jacobson,et al.  Alteration of poly(ADP-ribose) metabolism by hyperthermia. , 1984, Biochemical and biophysical research communications.

[80]  Alan Ashworth,et al.  Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy , 2005, Nature.

[81]  E. Wagner,et al.  PARP is important for genomic stability but dispensable in apoptosis. , 1997, Genes & development.

[82]  S. Hanai,et al.  Inhibition of Crm1–p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation , 2007, Nature Cell Biology.

[83]  M. Kawaichi,et al.  Natural occurrence of poly(ADP-ribosyl) histones in rat liver. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[84]  M. Jacobson,et al.  Poly(ADP-ribose) levels in carcinogen-treated cells , 1979, Nature.

[85]  T. Sugimura,et al.  Polymerization of the adenosine 5'-diphosphate ribose moiety of NAD by rat liver nuclear enzyme. , 1967, Biochimica et biophysica acta.

[86]  J. Węsierska‐Gądek,et al.  ADP-ribosylation of wild-type p53 in vitro: binding of p53 protein to specific p53 consensus sequence prevents its modification. , 1996, Biochemical and biophysical research communications.

[87]  M. Hottiger.  Nuclear ADP-Ribosylation and Its Role in Chromatin Plasticity, Cell Differentiation, and Epigenetics. , 2015, Annual review of biochemistry.

[88]  A. Caflisch,et al.  Macrodomain-containing proteins are new mono-ADP-ribosylhydrolases , 2013, Nature Structural &Molecular Biology.

[89]  E. Steinhagen-Thiessen,et al.  Mono(ADP-ribosyl)ation and poly(ADP-ribosyl)ation of proteins in developing liver and in hepatomas: relation of conjugate subfractions to metabolic competence and proliferation rates. , 1981, European journal of biochemistry.

[90]  V. Schreiber,et al.  Poly(ADP-ribose): novel functions for an old molecule , 2006, Nature Reviews Molecular Cell Biology.

[91]  L. Rubinstein,et al.  Preclinical Modeling of a Phase 0 Clinical Trial: Qualification of a Pharmacodynamic Assay of Poly (ADP-Ribose) Polymerase in Tumor Biopsies of Mouse Xenografts , 2008, Clinical Cancer Research.