Skip to main content
SpringerLink
Log in

Molecular mechanisms of transcriptional regulation by Poly(ADP-ribose) polymerase 1

  • Reviews
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

Poly-ADP-ribosylation is a covalent posttranslational modification of nuclear proteins that plays a key role in the immediate cell response to genotoxic stress. Poly(ADP-ribose) polymerases (PARPs) synthesize long and branched ADP-ribose polymers on acceptor regulatory proteins, thereby changing their activity. Poly-ADP metabolism regulates DNA repair, the cell cycle, replication, cell senescence and death, a remodeling of the chromatin structure, and gene transcription. PARP1 is one of the most common nuclear proteins and is responsible for producing ∼90% of all ADP-ribose polymers in the cell. PARP1 inhibitors are promising as antitumor agents. At the same time, current inhibitors targeting the catalytic domain of PARP1 have a number of side effects. Considering the potential benefits PARP1 inhibitors may offer for treating many diseases, it is necessary to develop new strategies of PARP1 inhibition. PARP1 has a modular structure and possesses catalytic, transcription, and DNA-binding activities. The review focuses primarily on the role PARP1 plays in regulating transcription. The structure and functional organization of PARP1 and multiple pathways of the PARP1-dependent transcriptional regulation at the levels of chromatin remodeling, DNA methylation, and transcription are considered in detail. Studying the molecular mechanisms that regulate these processes can provide a basis for a search and design of new PARP1 inhibitors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ATM:

ataxia telangiectasia mutated protease

CTCF:

CCCTC-binding factor

DNMT1:

DNA methyltransferase 1

FACT:

facilitates chromatin transcription

PARP:

poly(ADP-ribose) polymerase

PAR:

poly(ADP-ribose)

NAD:

nicotinamide adenine dinucleotide

ZF:

zinc finger

DSB:

double-strand break

HBC:

hepatitis B virus

iPSC:

induced pluripotent stem cell

References

  1. D’Amours D., Desnoyers S., D’Silva I., Poirier G.G. 1999. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem. J. 342, 249–268.

    PubMed Central  PubMed  Google Scholar 

  2. Haince J.F., McDonald D., Rodrigue A., Dery U., Masson J.Y., Hendzel M.J., Poirier G.G. 2008. PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites. J. Biol. Chem. 283, 1197–1208.

    CAS  PubMed  Google Scholar 

  3. Thomas C., Tulin A.V. 2013. Poly-ADP-ribose polymerase, machinery for nuclear processes. Mol. Aspects Med. 34, 1124–1137.

    CAS  PubMed  Google Scholar 

  4. Gibson B.A., Kraus W.L. 2012. New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs. Nat. Rev. Mol. Cell Biol. 13, 411–424.

    CAS  PubMed  Google Scholar 

  5. Hassa P.O., Hottiger M.O. 2002. The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders. Cell Mol. Life Sci. 59, 1534–1553.

    CAS  PubMed  Google Scholar 

  6. Ame J.C., Spenlehauer C., de Murcia G. 2004. The PARP superfamily. BioEssays. 26, 882–893.

    CAS  PubMed  Google Scholar 

  7. Ludwig A.B., Holtlund J., Hilz H. 1988. Immunoquantitation and size determination of intrinsic poly(ADP-ribose) polymerase from acid precipitates. An analysis of the in vivo status in mammalian species and in lower eukaryotes. J. Biol. Chem. 263, 6993–6999.

    CAS  PubMed  Google Scholar 

  8. Yamanaka H., Willis E.H, Wasson D.B., Carson D.A. 1988. Characterization of human poly(ADP-ribose) polymerase with autoantibodies. J. Biol. Chem. 263, 3879–3883.

    CAS  PubMed  Google Scholar 

  9. Bürkle A., Virag L. 2013. Poly(ADP-ribose), PARa-digms and PARadoxes. Mol. Aspects Med. 34, 1046–1065.

    PubMed  Google Scholar 

  10. Nishikimi M., Ogasawara K., Kameshita I., Taniguchi T., Shizuta Y. 1982. Poly(ADP-ribose) synthetase. The DNA binding domain and the automodification domain. J. Biol. Chem. 257, 6102–6105.

    CAS  PubMed  Google Scholar 

  11. Kameshita I., Matsuda Z., Taniguchi T., Shizuta Y. 1984. Poly(ADPRibose) synthetase. Separation and identification of three proteolytic fragments as the substrate-binding domain, the DNA-binding domain, and the automodification domain. J. Biol. Chem. 259, 4770–4776.

    CAS  PubMed  Google Scholar 

  12. Gradwohl G., de Murcia J. M., Molinete M., Simonin F., Koken M., Hoeijmakers J.H. 1990. The second zincfinger domain of poly(ADP-ribose) polymerase determines specificity for single-stranded breaks in DNA. Proc. Natl. Acad. Sci. U. S. A. 87, 2990–2994.

    PubMed Central  CAS  PubMed  Google Scholar 

  13. D’Silva P.J., Lagueux J., D’Amours D., Chaudhry M.A., Weinfeld M., Lees-Miller S.P., Poirier G.G. 1999. Relative affinities of poly(ADP-ribose) polymerase and DNA-dependent protein kinase for DNA strand interruptions. Biochim. Biophys. Acta. 1430, 119–126.

    PubMed  Google Scholar 

  14. Pion E.B., Stiegler P., Ullmann G.M., Mély Y., de Murcia G., Gérard D. 2003. Poly(ADP-ribose) polymerase-1 dimerizes at a 5’ recessed DNA end in vitro, a fluorescence study. Biochemistry. 42, 12409–11247.

    CAS  PubMed  Google Scholar 

  15. Lonskaya I., Shlyakhtenko L.S., Oussatcheva E.A., Lyubchenko Y.L., Soldatenkov V.A. 2005. Regulation of poly(ADP-ribose) polymerase-1 by DNA structurespecific binding. J. Biol. Chem. 280, 17076–17083.

    CAS  PubMed  Google Scholar 

  16. Ali A.A., Arribas-Bosacoma R., Kozlowski M., Hassa P.O., Hassler M., Ladurner A.G., Pearl L.H., Oliver A.W. 2012. The zinc-finger domains of PARP1 cooperate to recognize DNA strand breaks. Nat. Struct. Mol. Biol. 19, 685–692.

    CAS  PubMed  Google Scholar 

  17. Langelier M.F., Roy S., Pascal J.M. 2011. Crystal structures of poly(ADP-ribose) polymerase-1 (PARP-1) zinc fingers bound to DNA, structural and functional insights into DNA-dependent PARP-1 activity. J. Biol. Chem. 286, 10690–10701.

    PubMed Central  CAS  PubMed  Google Scholar 

  18. Langelier M.F., Roy S., Pascal J.M. 2012. Structural basis for DNA damage-dependent poly(ADP-ribosyl)ation by human PARP-1. Science. 336, 728–732.

    PubMed Central  CAS  PubMed  Google Scholar 

  19. Eustermann S., Yang J.C., Cole P.T., Gruszka D., Veprintsev D., Neuhaus D. 2011. The DNA-binding domain of humanPARP-1 interacts with DNAsinglestrand breaks as a monomer through its second zinc finger. J. Mol. Biol. 407, 149–170.

    PubMed Central  CAS  PubMed  Google Scholar 

  20. Pion E., Amé J.C., Gérard D., de Murcia G., Bombarda E. 2005. DNA-induced dimerization of poly(ADP-ribose) polymerase-1 triggers its activation. Biochemistry. 44, 14670–14681.

    CAS  PubMed  Google Scholar 

  21. Altmeyer M., Messner S., Hassa P.O., Fey M. Hottiger M.O. 2009. Molecular mechanism of poly(ADP-ribosyl)ation by PARP1 and identification of lysine residues as ADP-ribose acceptor sites. Nucleic Acids Res. 37, 3723–3738.

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Mendoza-Alvarez H., Alvarez-Gonzalez R. 1993. Poly(ADP-ribose) polymerase is a catalytic dimer and the automodification reaction is intermolecular. J. Biol. Chem. 268, 22575–22580.

    CAS  PubMed  Google Scholar 

  23. Bauer P.I., Buki K.G., Hakam A., Kun E. 1990. Macromolecular association of ADP-ribosyltransferase and its correlation with enzymic activity. Biochem J. 270, 17–26.

    PubMed Central  CAS  PubMed  Google Scholar 

  24. Schreiber V., Molinete M., Boeuf H., de Murcia G., Menissier-de Murcia J. 1992. The human poly(ADP-ribose) polymerase nuclear localization signal is a bipartite element functionally separate from DNA binding and catalytic activity. EMBO J. 11, 3263–3269.

    PubMed Central  CAS  PubMed  Google Scholar 

  25. Soldani C., Scovassi A.I. 2002. Poly(ADP-ribose) polymerase-1 cleavage during apoptosis, an update. Apoptosis. 7, 321–328.

    CAS  PubMed  Google Scholar 

  26. Langelier M.F., Servent K.M., Rogers E.E., Pascal J.M. 2008. A third zinc-binding domain of uman poly(ADP-ribose) polymerase-1 coordinates DNA-dependent enzyme activation. J. Biol. Chem. 283(7), 4105–4114.

    CAS  PubMed  Google Scholar 

  27. Tao Z., Gao P., Hoffman D.W., Liu H.W. 2008. Domain C of human poly(ADP-ribose) polymerase-1 is important for enzyme activity and contains a novel zinc-ribbon motif. Biochemistry. 47, 5804–5813.

    CAS  PubMed  Google Scholar 

  28. Langelier M.F., Planck J.L., Kraus W.L., Pascal J.M. 2010. The Zn3 domain of human poly(ADP-ribose) polymerase-1 (PARP1) functions in both DNA-dependent poly(ADP-ribose) synthesis activity and chromatin compaction. J. Biol. Chem. 285, 18877–18887.

    PubMed Central  CAS  PubMed  Google Scholar 

  29. Bork P., Hofmann K., Bucher P., Neuwald A.F., Altschul S.F., Koonin E.V. 1997. A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins. FASEB J. 11, 68–76.

    CAS  PubMed  Google Scholar 

  30. Masson M., Niedergang C., Schreiber V., Muller S., Menissier-de Murcia J., de Murcia G. 1998. XRCC1 is specifically associated with poly(ADPribose) polymerase and negatively regulates its activity following DNA damage. Mol. Cell Biol. 18, 3563–3571.

    PubMed Central  CAS  PubMed  Google Scholar 

  31. Masson M., Menissier-de Murcia J., Mattei M.G., de Murcia G., Niedergang C.P. 1997. Poly(ADP-ribose) polymerase interacts with a novel human ubiquitin conjugating enzyme, hUbc9. Gene. 190, 287–296.

    CAS  PubMed  Google Scholar 

  32. Buki K.G., Bauer P.I., Hakam A., Kun E. 1995. Identification of domains of poly(ADP-ribose) polymerase for protein binding and selfassociation. J. Biol. Chem. 270, 3370–3377.

    CAS  PubMed  Google Scholar 

  33. Nie J., Sakamoto S., Song D., Qu Z., Ota K., Taniguchi T. 1998. Interaction of Oct-1 and automodification domain of poly(ADP-ribose) synthetase. FEBS Lett. 424, 27–32.

    CAS  PubMed  Google Scholar 

  34. Griesenbeck J., Ziegler M., Tomilin N., Schweiger M., Oei S.L. 1999. Stimulation of the catalytic activity of poly(ADP-ribosyl) transferase by transcription factor Yin Yang 1. FEBS Lett. 443, 20–24.

    CAS  PubMed  Google Scholar 

  35. Semighini C.P., Savoldi M., Goldman G.H., Harris S.D. 2006. Functional characterization of the putative Aspergillus nidulans poly(ADP-ribose) polymerase homolog PrpA. Genetics. 173, 87–98.

    PubMed Central  CAS  PubMed  Google Scholar 

  36. Simonin F., Menissier-de Murcia J., Poch O., Muller S., Gradwohl G., Molinete M., Penning C., Keith G., de Murcia G. 1990. Expression and site-directed mutagenesis of the catalytic domain of human poly(ADPribose) polymerase in Escherichia coli: Lysine 893 is critical for activity. J. Biol. Chem. 265, 19249–19256.

    CAS  PubMed  Google Scholar 

  37. de Murcia G., Menissier de Murcia J. 1994. Poly(ADP-ribose) polymerase, a molecular nick-sensor. Trends Biochem. Sci. 19, 172–176.

    PubMed  Google Scholar 

  38. Ruf A., de Murcia G., Schulz G.E. 1998. Inhibitor and NAD+ binding to poly(ADP-ribose) polymerase as derived from crystal structures and homology modeling. Biochemistry. 37, 3893–3900.

    CAS  PubMed  Google Scholar 

  39. Marsischky G.T., Wilson B.A., Collier R.J. 1995. Role of glutamic acid 988 of human poly-ADP-ribose polymerase in polymer formation. Evidence for active site similarities to the ADP-ribosylating toxins. J. Biol. Chem. 270, 3247–3254.

    CAS  Google Scholar 

  40. Alvarez-Gonzalez R., Althaus F.R. 1989. Poly(ADP-ribose) catabolism in mammalian cells exposed to DNA-damaging agents. Mutat. Res. 218, 67–74.

    CAS  PubMed  Google Scholar 

  41. Griesenbeck J., Mayer-Kuckuk P., Ziegler M., Buchlow G., Schweiger M. 1997. Protein-protein interaction of the human poly(ADP-ribosyl)transferase depends on the functional state of the enzyme. Biochemistry. 36, 7297–7304.

    CAS  PubMed  Google Scholar 

  42. Ruscetti T.L., Halbrook J., Trong H., Hoekstra M.F., Chen D.J., Peterson S.R. 1998. Stimulation of the DNA-dependent protein kinase by poly(ADP-ribose) polymerase. J. Biol. Chem. 273, 14461–14467.

    CAS  PubMed  Google Scholar 

  43. Kumari S.R., Mendoza-Alvarez H., Alvarez-Gonzalez R. 1998. Functional interactions of p53 with poly(ADP-ribose) polymerase (PARP) during apoptosis following DNA damage, covalent poly(ADP-ribosyl)ation of p53 by exogenous PARP and noncovalent binding of p53 to the M(r) 85,000 proteolytic fragment. Cancer Res. 58, 5075–5078.

    CAS  PubMed  Google Scholar 

  44. Kun E., Kirsten E., Mendeleyev J., Ordahl C.P. 2004. Regulation of the enzymatic catalysis of poly(ADP-ribose) polymerase by dsDNA, polyamines, Mg2+, Ca2+, histones H1 and H3, and ATP. Biochemistry. 43, 210–216.

    CAS  PubMed  Google Scholar 

  45. Tulin A., Spradling A. 2003. Chromatin loosening by poly(ADP)-ribose polymerase (PARP) at Drosophila puff loci. Science. 299, 560–562.

    CAS  PubMed  Google Scholar 

  46. Ji Y., Tulin A. 2010. The roles of PARP1 in gene control and cell differentiation. Curr. Opin. Genet. Dev. 20, 512–518.

    PubMed Central  CAS  PubMed  Google Scholar 

  47. Frizzell K.M., Berrocal J.G., Zhang T., Krishnakumar R., Cen Y., Sauve A.A., Kraus W.L. 2009. Global analysis of transcriptional regulation by poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in MCF-7 human breast cancer cells. J. Biol. Chem. 284, 33926–33938.

    PubMed Central  CAS  PubMed  Google Scholar 

  48. Ogino H.N., Gunji A., Maeda M., Suzuki H., Ohta T., Murakami Y., Nakagama H., Sugimura T., Masutani M. 2007. Loss of PARP-1 affects gene expression profile in a genome-wide manner in es cells and liver cells. BMC Genomics. 8, 41.

    PubMed Central  PubMed  Google Scholar 

  49. Kraus W.L., Hottiger M.O. 2013. PARP-1 and gene regulation: Progress and puzzles. Mol. Aspects Med. 34, 1109–1123.

    CAS  PubMed  Google Scholar 

  50. Poirier G.G., de Murcia G., Jongstra-Bilen J., Niedergang C., Mandel P. 1982. Poly(ADP-ribosyl)ation of polynucleosomes causes relaxation of chromatin structure. Proc. Natl. Acad. Sci. U. S. A. 79, 3423–3427.

    PubMed Central  CAS  PubMed  Google Scholar 

  51. Kim M.Y., Mauro S., Gevry N., Lis J.T., Kraus W.L. 2004. NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1. Cell. 119, 803–814.

    CAS  PubMed  Google Scholar 

  52. Krishnakumar R., Gamble M., Frizzell K., Berrocal J., Kininis M., Kraus W. 2008. Reciprocal binding of PARP-1 and histone H1 at promoters specifies transcriptional outcomes. Science. 319, 819–821.

    CAS  PubMed  Google Scholar 

  53. Krishnakumar R., Kraus W.L. 2010b. PARP-1 regulates chromatin structure and transcription through a KDM5B-dependent pathway. Mol. Cell. 39, 736–749.

    PubMed Central  CAS  PubMed  Google Scholar 

  54. Krishnakumar R., Kraus W.L. 2010a. The PARP side of the nucleus, molecular actions, physiological outcomes, and clinical targets. Mol. Cell. 39, 8–24.

    PubMed Central  CAS  PubMed  Google Scholar 

  55. Wright R.H., Castellano G., Bonet J., Le Dily F., Font-Mateu J., Ballare C., Nacht A.S., Soronellas D., Oliva B., Beato M. 2012. CDK2-dependent activation of PARP-1 is required for hormonal gene regulation in breast cancer cells. Genes Dev. 26, 1972–1983.

    PubMed Central  CAS  PubMed  Google Scholar 

  56. Kraus W.L., Lis J.T. 2003. PARP goes transcription. Cell. 113, 677–683.

    CAS  PubMed  Google Scholar 

  57. Martinez-Zamudio R., Ha H.C. 2012. Histone ADP-ribosylation facilitates gene transcription by directly remodeling nucleosomes. Mol. Cell. Biol. 32, 2490–2502.

    PubMed Central  CAS  PubMed  Google Scholar 

  58. Rouleau M.A., Poirier G.G. 2004. Poly(ADP-ribosyl)ated chromatin domains. J. Cell Sci. 117, 815–825.

    CAS  PubMed  Google Scholar 

  59. Messner S., Altmeyer M., Zhao H., Pozivil A., Roschitzki B., Gehrig P., Rutishauser D., Huang D., Caflisch A., Hottiger M. 2010. PARP1 ADP-ribosylates lysine residues of the core histone tails. Nucleic Acids Res. 38, 6350–6362.

    PubMed Central  CAS  PubMed  Google Scholar 

  60. Pinnola A., Naumova N., Shah M., Tulin A.V. 2007. Nucleosomal core histones mediate dynamic regulation of poly(ADP-ribose) polymerase 1 protein binding to chromatin and induction of its enzymatic activity. J. Biol. Chem. 282, 32511–32119.

    CAS  PubMed  Google Scholar 

  61. Bryant H.E., Thomas H.D., Parker K.M., Flower D., Lopez E., Kyle S., Meuth M., Curtin N.J., Helleday T. 2005. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 434, 913–917.

    CAS  PubMed  Google Scholar 

  62. Nazarov I.B., Krutilina R.I., Svetlova M.P., Solovjeva L.V., Nikiforov A.A., Oei S.L., Zalenskaya I.A., Yau P.M., Bradbury E.M., Tomilin N.V. 2003. Dephosphorylation of histone gamma-H2AX during repair of DNA double-strand breaks in mammalian cells and its inhibition by calyculin A. Radiat. Res. 160, 309–317.

    CAS  PubMed  Google Scholar 

  63. Svetlova M., Nishi K., Nazarov I., Siino J., Tomilin N. 2007. Elimination of radiation-induced gamma-H2AX foci in mammalian nucleus can occur by histone exchange. Biochem. Biophys. Res. Commun. 358, 650–654.

    CAS  PubMed  Google Scholar 

  64. Meyer-Ficca M.L., Bürkle A., Meyer R.G. 2005. Poly(ADP-ribosyl)ation during chromatin remodeling steps in rat spermiogenesis. Chromosoma. 114, 67–74.

    CAS  PubMed  Google Scholar 

  65. Du Y.C., Gu S., Zhou J., Wang T., Cai H., Macinnes M.A., Bradbury E.M., Chen X. 2006. The dynamic alterations of H2AX complex during DNA repair detected by a proteomic approach reveal the critical roles of Ca2+/Calmodulin in the ionizing radiation-induced cell cycle arrest. Mol. Cell. Proteomics. 5, 1033–1044.

    CAS  PubMed  Google Scholar 

  66. Haince J., Dawson V.L., Dawson T.M., Hendzel M.J., Lavin M.F., Poirier G.G. 2007. Ataxia telangiectasia mutated (ATM) signaling network is modulated by a novel poly(ADP-ribose)-dependent pathway in the early response to DNA-damaging agents. J. Biol. Chem. 282, 16441–16453.

    CAS  PubMed  Google Scholar 

  67. Kotova E., Lodhi N., Jarnik M., Pinnola A.D., Ji Y. Tulin A.V. 2011. Drosophila histone H2A variant (H2Av) controls poly(ADP-ribose) polymerase 1 (PARP1) activation in chromatin. Proc. Natl. Acad. Sci. U. S. A. 108, 6205–6210.

    PubMed Central  CAS  PubMed  Google Scholar 

  68. Henikoff S., Sakai A., Loeb G.B., Ahmad K. 2009. Genome-wide profiling of salt fractions maps physical properties of chromatin. Genome Res. 19, 460–469.

    PubMed Central  CAS  PubMed  Google Scholar 

  69. Kumar S.V., Wigge P.A. 2010. H2A.Z-containing nucleosomes mediate the thermosensory response in Arabidopsis. Cell. 140, 136–147.

    CAS  PubMed  Google Scholar 

  70. Suto R.K., Clarkson M.J., Tremethick D.J., Luger K. 2000. Crystal structure of a nucleosome core particle containing the variant histone H2A.Z. Nat. Struct. Biol. 7, 1121–1124.

    CAS  PubMed  Google Scholar 

  71. Kusch T., Florens L., Macdonald W.H., Swanson S.K., Glaser R.L., Yates J.R., Abmayr S.M., Washburn M.P., Workman J.L. 2004. Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions. Science. 306, 2084–2087.

    CAS  PubMed  Google Scholar 

  72. O’Donnell A., Yang S.H., Sharrocks A.D. 2013. PARP1 orchestrates variant histone exchange in signal-mediated transcriptional activation. EMBO Rep. 12, 1084–1091.

    Google Scholar 

  73. Gottschalk A.J., Timinszky G., Kong S.E., Jin J., Cai Y., Swanson S.K., Washburn M.P., Florens L., Ladurner A.G., Conaway J.W., Conaway R.C. 2009. Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler. Proc. Natl. Acad. Sci. U. S. A. 106, 13770–13774.

    PubMed Central  CAS  PubMed  Google Scholar 

  74. Gao F.K., Kwon S.W., Zhao Y., Jin Y. 2009. Parp1 poly(ADP-ribosyl)ates Sox2 to control Sox2 protein levels and FGF4 expression during embryonic stem cell differentiation. J. Biol. Chem. 284, 22263–22273.

    PubMed Central  CAS  PubMed  Google Scholar 

  75. Lonn P., Dahl M., Hellman U., Heldin C.H., Moustakas A. 2010. PARP-1 attenuates Smad-mediated transcription. Mol. Cell. 40, 521–532.

    PubMed  Google Scholar 

  76. Zaniolo K.D., Leclerc S., Guerin S.L. 2007. Regulation of poly(ADP-ribose) polymerase-1 (PARP-1) gene expression through the post-translational modification of SP1, a nuclear target protein of PARP-1. BMC Mol. Biol. 8, 96.

    PubMed Central  PubMed  Google Scholar 

  77. Huang D.Y., Yang C., Wang Y., Liao Y., Huang K. 2009. PARP-1 suppresses adiponectin expression through poly(ADP-ribosyl)ation of PPAR gamma in cardiac fibroblasts. Cardiovasc. Res. 81, 98–107.

    CAS  PubMed  Google Scholar 

  78. Zerfaoui M., Naura A.S., Suzuki Y., Kim H., Ju J., Liu T., Hans C.P., Kim J.G., Abd Elmageed Z.Y. 2010. Poly(ADP-ribose) polymerase-1 is a determining factor in crm1-mediated nuclear export and retention of p65 NF-kappa B upon TLR4 stimulation. J. Immunol. 185, 1894–1902.

    PubMed Central  CAS  PubMed  Google Scholar 

  79. Hassa P.O., Haenni S.S., Buerki C., Meier N.I., Lane W.S., Owen H., Gersbach M., Imhof R., Hottiger M.O. 2005. Acetylation of PARP-1 by p300/CBP regulates coactivation of NF-kappa B-dependent transcription. J. Biol. Chem. 280, 40450–40464.

    CAS  PubMed  Google Scholar 

  80. Messner S.S., Altmeyer M., Kassner I., Schmidt D., Schar P., Muller S., Hottiger M.O. 2009. Sumoylation of poly(ADP-ribose) polymerase 1 inhibits its acetylation and restrains transcriptional coactivator function. FASEB J. 23, 3978–3989.

    CAS  PubMed  Google Scholar 

  81. Oei S.L., Griesenbeck J., Schweger M., Ziegler M. 1998. Regulation of RNA polymerase II-dependent transcription by poly(ADP-ribosyl)ation of transcription factors. J. Biol. Chem. 273, 31644–31647.

    CAS  PubMed  Google Scholar 

  82. Sala A., La Rocca G., Burgio G., Kotova E., Di Gesu D., Collesano M., Ingrassia A.M., Tulin A.V., Corona D.F. 2008. The nucleosome-remodeling ATPase ISWI is regulated by poly-ADP-ribosylation. PLoS Biol. 6, e252.

    PubMed  Google Scholar 

  83. Huang J.Y., Chang Y.L., Wang H.T., Chuang W.T., Lee S.C. 2006. Modulation of nucleosome-binding activity of FACT by poly(ADP-ribosyl)ation. Nucleic Acids Res., 34, 2398–2407.

    PubMed Central  CAS  PubMed  Google Scholar 

  84. Pavri R., Lewis B., Kim T.K., Dilworth F.J., Erdjument-Bromage H., Tempst P., de Murcia G., Evans R., Chambon P., Reinberg D. 2005. PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator. Mol. Cell. 18, 83–96.

    CAS  PubMed  Google Scholar 

  85. Ju B., Song E.J., Lee K.J., Rose D.W., Glass C.K., Rosenfeld M.G. 2004. Activating the PARP-1 sensor component of the groucho/TLE1 corepressor complex mediates a camkinase II delta-dependent neurogenic gene activation pathway. Cell. 119, 815–829.

    CAS  PubMed  Google Scholar 

  86. Ju B., Perissi V., Garcia-Bassets I., Rose D.W., Glass C.K., Rosenfeld M.G. 2006. A topoisomerase II beta-mediated dsdna break required for regulated transcription. Science. 312, 1798–1802.

    CAS  PubMed  Google Scholar 

  87. Slattery E., Dignam J.D., Matsui T., Roeder R.G. 1983. Purification and analysis of a factor which suppresses nick-induced transcription by RNA polymerase II and its identity with poly(ADP-ribose) polymerase. J. Biol. Chem. 258, 5955–5959.

    CAS  PubMed  Google Scholar 

  88. Meisterernst M., Stelzer G., Roeder R.G. 1997. Poly(ADP-ribose) polymerase enhances activatordependent transcription in vitro. Proc. Natl. Acad. Sci. U. S. A. 94, 2261–2265.

    PubMed Central  CAS  PubMed  Google Scholar 

  89. Reale A., Matteis G.D., Galleazzi G., Zampieri M., Caiafa P. 2005. Modulation of DNMT1 activity by ADP-ribose polymers. Oncogene. 24, 13–19.

    CAS  PubMed  Google Scholar 

  90. Attwood J.T., Yung R.L., Richardson B.C. 2002. DNA methylation and the regulation of gene transcription. Cell. Mol. Life Sci. 59, 241–257.

    CAS  PubMed  Google Scholar 

  91. Caiafa P., Zampieri M. 2005. DNA methylation and chromatin structure, the puzzling CpG islands. J. Cell. Biochem. 94, 257–265.

    CAS  PubMed  Google Scholar 

  92. Caiafa P., Guastafierro T., Zampieri M. 2009. Epigenetics, poly(ADP-ribosyl)ation of PARP-1 regulates genomic methylation patterns. FASEB J. 23, 672–678.

    CAS  PubMed  Google Scholar 

  93. Caiafa P., Zlatanova J. 2009. CCCTC-binding factor meets poly(ADP-ribose) polymerase-1. J. Cell. Physiol. 219, 265–270.

    CAS  PubMed  Google Scholar 

  94. Guastafierro T., Cecchinelli B., Zampieri M., Reale A., Riggio G., Sthandier O., Zupi G., Calabrese L., Caiafa P. 2008. CCCTC-binding factor activates PARP-1 affecting DNA methylation machinery. J. Biol. Chem. 283, 21873–21880.

    PubMed Central  CAS  PubMed  Google Scholar 

  95. Zampieri M., Guastafierro T., Calabrese R., Ciccarone F., Bacalini M.G., Reale A., Perilli M., Passananti C., Caiafa P. 2012. ADP-ribose polymers localized on Ctcf-Parp1-Dnmt1 complex prevent methylation of Ctcf target sites. Biochem. J. 441, 645–652.

    PubMed Central  CAS  PubMed  Google Scholar 

  96. Vitale A. M., Wolvetang E., Mackay-Sim A. 2011. Induced pluripotent stem cells, a new technology to study human diseases. Int. J. Biochem. Cell. Biol. 43, 843–846.

    CAS  PubMed  Google Scholar 

  97. Doege C.A., Inoue K., Yamashita T., Rhee D.B., Travis S., Fujita R., Guarnieri P., Bhagat G., Vanti W.B., Shih A., Levine R.L., Nik S., Chen E.I., Abeliovich A. 2012. Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2. Nature. 488, 652–655.

    CAS  PubMed  Google Scholar 

  98. Ko H.L., Ren E.C. 2012. Functional aspects of PARP1 in DNA repair and transcription. Biomolecules. 2, 524–548.

    PubMed Central  CAS  PubMed  Google Scholar 

  99. Maruyama T.N., Yoshikawa H., Suzuki N. 2007. Txk, a member of the non-receptor tyrosine kinase of the tec family, forms a complex with poly(ADP-ribose) polymerase 1 and elongation factor 1alpha and regulates interferon-gamma gene transcription in Th1 cells. Clin. Exp. Immunol. 147, 164–175.

    PubMed Central  CAS  PubMed  Google Scholar 

  100. Kang X., Kim H.J., Ramirez M., Salameh S., Ma X. 2010. The septic shock-associated Il-10 −1082 A > G polymorphism mediates allele-specific transcription via poly(ADP-ribose) polymerase 1 in macrophages engulfing apoptotic cells. J. Immunol. 184, 3718–3724.

    PubMed Central  CAS  PubMed  Google Scholar 

  101. Zhang Z.H., Simbulan-Rosenthal C.M., Anderson M.G. 2002. Sequence-specific binding of poly(ADP-ribose) polymerase-1 to the human T cell leukemia virus type-I tax responsive element. Virology. 296, 107–116.

    CAS  PubMed  Google Scholar 

  102. Wang J.B., Li J., Couch F.J., Wu K., Zhao R.C. 2008. Poly(ADP-ribose) polymerase-1 down-regulates BRCA2 expression through the BRCA2 promoter. J. Biol. Chem. 283, 36249–36256.

    PubMed Central  CAS  PubMed  Google Scholar 

  103. Zhou J., Poon V.K., Chen D.Q., Chan C.C., Ng F., Guan X.Y., Watt R.M., Lu L., Yuen K.Y. 2009. Functional dissection of an IFN-alpha/beta receptor 1 promoter variant that confers higher risk to chronic hepatitis B virus infection. J. Hepatol. 51, 322–332.

    CAS  PubMed  Google Scholar 

  104. Pottier N.C., Yang W., Assem M., Tracey L., Obenauer J.C., Panetta J.C., Relling M.V., Evans W.E. 2007. Expression of SMARCB1 modulates steroid sensitivity in human lymphoblastoid cells. Identification of a promoter SNP that alters PARP1 binding and SMARCB1 expression. Hum. Mol. Genet. 16, 2261–2271.

    Google Scholar 

  105. Ko H.L., Ren E.C. 2011. Novel poly(ADP-ribose) polymerase 1 binding motif in hepatitis B virus core promoter impairs DNA damage repair. Hepatology. 54, 1190–1198.

    CAS  PubMed  Google Scholar 

  106. Kotova E., Jarnik M., Tulin A.V. 2010. Uncoupling of the transactivation and transrepression functions of PARP1 protein. Proc. Natl. Acad. Sci. U. S. A. 107, 6406–6411.

    PubMed Central  CAS  PubMed  Google Scholar 

  107. Huang K. 2004. Analysis of nucleotide sequence-dependent DNA binding of poly(ADP-ribose) polymerase in a purified system. Biochemistry. 43, 217–223.

    CAS  PubMed  Google Scholar 

  108. Dantzer F., Santoro R. 2013. The expanding role of PARPs in the establishment and maintenance of heterochromatin. Review. FEBS J. 280, 3508–3518.

    CAS  PubMed  Google Scholar 

  109. Hassa P., Covic M., Hasan S., Imhof R., Hottiger M. 2001. The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function. J. Biol. Chem. 276, 45588–45597.

    CAS  PubMed  Google Scholar 

  110. Pétrilli V., Herceg Z., Hassa P., Patel N., Di Paola R., Cortes U., Dugo L., Filipe H.-M., Thiemermann C., Hottiger M., Cuzzocrea S., Wang Z.-Q. 2004. Noncleavable poly(ADP-ribose) polymerase-1 regulates the inflammation response in mice. J. Clin. Invest. 114, 1072–1081.

    PubMed Central  PubMed  Google Scholar 

  111. Carrillo A., Monreal Y., Ramírez P., Marin L., Parrilla P., Oliver F., Yélamos J. 2004. Transcription regulation of TNF-alpha-early response genes by poly(ADPribose) polymerase-1 in murine heart endothelial cells. Nucleic Acids Res. 32, 757–766.

    PubMed Central  CAS  PubMed  Google Scholar 

  112. Robert I., San Martin B.R., Schreiber V., Dantzer F. 2013. Functional aspects of PARylation in induced and programmed DNA repair processes: Preserving genome integrity and modulating physiological events. Mol. Aspects Med. 34, 1138–1152.

    CAS  PubMed  Google Scholar 

  113. Luo X., Kraus W.L. 2012. On PAR with PARP, cellular stress signaling through poly(ADP-ribose) and PARP-1. Genes Dev. 26, 417–432.

    PubMed Central  PubMed  Google Scholar 

  114. Chou D., Dephoure N.E., Tan X., Nottke A.C., Hurov K.E., Gygi S.P., Colaiacovo M.P., Elledge S.J. 2010. A chromatin localization screen reveals poly(ADP ribose)-regulated recruitment of the repressive polycomb and NuRD complexes to sites of DNA damage. Proc. Natl. Acad. Sci. U. S. A. 107, 18475–18480.

    PubMed Central  CAS  PubMed  Google Scholar 

  115. Nyquist P., De Graba T.J. 2009. The −928 G/C and — 362 G/C single-nucleotide polymorphisms in the promoter of MCP-1, Increased transcriptional activity and novel binding sites. Cerebrovasc. Dis. 29, 242–247.

    PubMed  Google Scholar 

  116. Akiyama T., Nata K., Kobayashi S., Abe M., Shervani N.J., Ikeda T., Nakagawa K., Unno M., Matsuno S. 2001. Activation of Reg gene, a gene for insulin-producing beta-cell regeneration: Poly(ADP-ribose) polymerase binds Reg promoter and regulates the transcription by auto poly(ADP-ribosyl)ation. Proc. Natl. Acad. Sci. U. S. A. 98, 48–53.

    PubMed Central  CAS  PubMed  Google Scholar 

  117. Mabley J., Murthy K.G., Zsengeller Z., Vaslin A., Benko R., Kollai M., Szabo C. 2005. Gender differences in the endotoxin-induced inflammatory and vascular responses: Potential role of poly(ADP-ribose) polymerase activation. J. Pharmacol. Exp. Ther. 315, 812–820.

    CAS  PubMed  Google Scholar 

  118. Liu T., Xiong H., Chen T.Y., Ni Z.P., Luo J.F., Zhao N.Q., Shen X.Z. 2008. A case-control study of the relationship between hepatitis B virus DNA level and risk of hepatocellular carcinoma in Qidong, China. World J. Gastroenterol. 14, 3059–3063.

    PubMed Central  PubMed  Google Scholar 

  119. Chan H.L.W., Wong G.L., Chim A.M., Lai L.H., Sung J.J. 2009. Evaluation of impact of serial hepatitis B virus DNA levels on development of hepatocellular carcinoma. J. Clin. Microbiol. 47, 1830–1836.

    PubMed Central  CAS  PubMed  Google Scholar 

  120. Kwon J.H., Jang J.W., Bae S.H., Yoon S.K., Yang J.M., Han N.I., Lee C.D., Lee Y.S., Chung K.W. 2009. Impact of serial hepatitis B virus DNA on hepatocellular carcinoma development in patients with liver cirrhosis. Intervirology. 53, 111–118.

    PubMed  Google Scholar 

  121. Hagen T.M., Curnutte J., Fowler P., Martinez V., Wehr C.M., Ames B.N., Chisari F.V. 1994. Extensive oxidative DNA damage in hepatocytes of transgenic mice with chronic active hepatitis destined to develop hepatocellular carcinoma. Proc. Natl. Acad. Sci. U. S. A. 91, 12808–12812.

    PubMed Central  CAS  PubMed  Google Scholar 

  122. Ohsaki E.U., Sakakibara S., Do E., Yada K., Yamanishi K. 2004. Poly(ADP-ribose) polymerase 1 binds to Kaposi’s sarcoma-associated herpesvirus (KSHV) terminal repeat sequence and modulates KSHV replication in latency. J. Virol. 78, 9936–9946.

    PubMed Central  CAS  PubMed  Google Scholar 

  123. Wang Y., Tang Q., Maul G.G., Yuan Y. 2008. Kaposi’s sarcoma-associated herpesvirus ori-Lyt-dependent DNA replication: Involvement of host cellular factors. J. Virol. 82, 2867–2882.

    PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biological Faculty, Moscow State University, Moscow, 119991, Russia

    N. V. Maluchenko, O. I. Kulaeva, A. A. Chupyrkina, D. V. Nikitin, M. P. Kirpichnikov & V. M. Studitsky

  2. Fox Chase Cancer Center, Philadelphia, PA, 19111-2497, USA

    O. I. Kulaeva, E. Yu. Kotova & V. M. Studitsky

  3. Skriabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia

    D. V. Nikitin

Authors
  1. N. V. Maluchenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. I. Kulaeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Yu. Kotova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. A. Chupyrkina
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. V. Nikitin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. P. Kirpichnikov
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. V. M. Studitsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. V. Maluchenko.

Additional information

Original Russian Text © N.V. Maluchenko, O.I. Kulaeva, E.Yu. Kotova, A.A. Chupyrkina, D.V. Nikitin, M.P. Kirpichnikov, V.M. Studitsky, 2015, published in Molekulyarnaya Biologiya, 2015, Vol. 49, No. 1, pp. 99–113.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maluchenko, N.V., Kulaeva, O.I., Kotova, E.Y. et al. Molecular mechanisms of transcriptional regulation by Poly(ADP-ribose) polymerase 1. Mol Biol 49, 86–98 (2015). https://doi.org/10.1134/S0026893315010094

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893315010094

Keywords

Search

Navigation