New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs - Nature Reviews Molecular Cell Biology
- ️Kraus, W. Lee
- ️Wed Jun 20 2012
Hassa, P. O., Haenni, S. S., Elser, M. & Hottiger, M. O. Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going? Microbiol. Mol. Biol. Rev. 70, 789–829 (2006).
Hassa, P. O. & Hottiger, M. O. The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases. Front. Biosci. 13, 3046–3082 (2008).
Schreiber, V., Dantzer, F., Ame, J. C. & de Murcia, G. Poly(ADP-ribose): novel functions for an old molecule. Nature Rev. Mol. Cell Biol. 7, 517–528 (2006).
Krishnakumar, R. & Kraus, W. L. The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets. Mol. Cell 39, 8–24 (2010).
Luo, X. & Kraus, W. L. On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1. Genes Dev. 26, 417–432 (2012).
Hassa, P. O. & Hottiger, M. O. The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-κB in inflammatory disorders. Cell. Mol. Life Sci. 59, 1534–1553 (2002).
Kraus, W. L. Transcriptional control by PARP-1: chromatin modulation, enhancer-binding, coregulation, and insulation. Curr. Opin. Cell Biol. 20, 294–302 (2008).
Ji, Y. & Tulin, A. V. The roles of PARP1 in gene control and cell differentiation. Curr. Opin. Genet. Dev. 20, 512–518 (2010).
Kim, M. Y., Zhang, T. & Kraus, W. L. Poly(ADP-ribosyl)ation by PARP-1: 'PAR-laying' NAD+ into a nuclear signal. Genes Dev. 19, 1951–1967 (2005).
Cohen-Armon, M. PARP-1 activation in the ERK signaling pathway. Trends Pharmacol. Sci. 28, 556–560 (2007).
Rouleau, M., Patel, A., Hendzel, M. J., Kaufmann, S. H. & Poirier, G. G. PARP inhibition: PARP1 and beyond. Nature Rev. Cancer 10, 293–301 (2010).
Sodhi, R. K., Singh, N. & Jaggi, A. S. Poly(ADP-ribose) polymerase-1 (PARP-1) and its therapeutic implications. Vascul. Pharmacol. 53, 77–87 (2010).
Underhill, C., Toulmonde, M. & Bonnefoi, H. A review of PARP inhibitors: from bench to bedside. Ann. Oncol. 22, 268–279 (2011).
Telli, M. L. PARP inhibitors in cancer: moving beyond BRCA. Lancet Oncol. 12, 827–828 (2011).
Hottiger, M. O., Hassa, P. O., Luscher, B., Schuler, H. & Koch-Nolte, F. Toward a unified nomenclature for mammalian ADP-ribosyltransferases. Trends Biochem. Sci. 35, 208–219 (2010).
Ame, J. C. et al. PARP-2, a novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase. J. Biol. Chem. 274, 17860–17868 (1999).
Boehler, C. et al. Poly(ADP-ribose) polymerase 3 (PARP3), a newcomer in cellular response to DNA damage and mitotic progression. Proc. Natl Acad. Sci. USA 108, 2783–2788 (2011).
Rulten, S. L. et al. PARP-3 and APLF function together to accelerate nonhomologous end-joining. Mol. Cell 41, 33–45 (2011).
Sbodio, J. I. & Chi, N. W. Identification of a tankyrase-binding motif shared by IRAP, TAB182, and human TRF1 but not mouse TRF1. NuMA contains this RXXPDG motif and is a novel tankyrase partner. J. Biol. Chem. 277, 31887–31892 (2002).
Loseva, O. et al. PARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the absence of DNA. J. Biol. Chem. 285, 8054–8060 (2010).
Aguiar, R. C., Takeyama, K., He, C., Kreinbrink, K. & Shipp, M. A. B-aggressive lymphoma family proteins have unique domains that modulate transcription and exhibit poly(ADP-ribose) polymerase activity. J. Biol. Chem. 280, 33756–33765 (2005).
Kleine, H. et al. Substrate-assisted catalysis by PARP10 limits its activity to mono-ADP-ribosylation. Mol. Cell 32, 57–69 (2008).
Kiehlbauch, C. C., Aboul-Ela, N., Jacobson, E. L., Ringer, D. P. & Jacobson, M. K. High resolution fractionation and characterization of ADP-ribose polymers. Anal. Biochem. 208, 26–34 (1993).
Ruf, A., Rolli, V., de Murcia, G. & Schulz, G. E. The mechanism of the elongation and branching reaction of poly(ADP-ribose) polymerase as derived from crystal structures and mutagenesis. J. Mol. Biol. 278, 57–65 (1998).
Ruf, A., de Murcia, G. & Schulz, G. E. Inhibitor and NAD+ binding to poly(ADP-ribose) polymerase as derived from crystal structures and homology modeling. Biochemistry 37, 3893–3900 (1998).
Otto, H. et al. In silico characterization of the family of PARP-like poly(ADP-ribosyl)transferases (pARTs). BMC Genom. 6, 139 (2005).
Bell, C. E. & Eisenberg, D. Crystal structure of diphtheria toxin bound to nicotinamide adenine dinucleotide. Biochemistry 35, 1137–1149 (1996).
Meyer-Ficca, M. L., Meyer, R. G., Coyle, D. L., Jacobson, E. L. & Jacobson, M. K. Human poly(ADP-ribose) glycohydrolase is expressed in alternative splice variants yielding isoforms that localize to different cell compartments. Exp. Cell Res. 297, 521–532 (2004).
Slade, D. et al. The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase. Nature 477, 616–620 (2011). Describes the structure of a bacterial homologue of PARG, and the surprising finding that PARG enzymes are structurally related to macrodomains. Infers the mechanistic details of PAR degradation from this structure and mutational analyses.
Miwa, M., Tanaka, M., Matsushima, T. & Sugimura, T. Purification and properties of glycohydrolase from calf thymus splitting ribose-ribose linkages of poly(adenosine diphosphate ribose). J. Biol. Chem. 249, 3475–3482 (1974).
Oka, S., Kato, J. & Moss, J. Identification and characterization of a mammalian 39-kDa poly(ADP-ribose) glycohydrolase. J. Biol. Chem. 281, 705–713 (2006).
Ono, T., Kasamatsu, A., Oka, S. & Moss, J. The 39-kDa poly(ADP-ribose) glycohydrolase ARH3 hydrolyzes O-acetyl-ADP-ribose, a product of the Sir2 family of acetyl-histone deacetylases. Proc. Natl Acad. Sci. USA 103, 16687–16691 (2006).
Niere, M. et al. ADP-ribosylhydrolase 3 (ARH3), not poly-ADP-ribose glycohydrolase (PARG) isoforms, are responsible for degradation of mitochondrial matrix-associated poly-ADP-ribose. J. Biol. Chem. 20 Mar 2012 (doi: 10.1074/jbc.M112.349183).
McLennan, A. G. The Nudix hydrolase superfamily. Cell. Mol. Life Sci. 63, 123–143 (2006).
Langelier, M. F., Planck, J. L., Roy, S. & Pascal, J. M. 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 (2011). Reports the structure of most of human PARP1 in complex with a model substrate for DNA double-strand break recognition. This work elucidates the inter-domain conformational changes that induce the activation of PARP1 catalytic activity following DNA substrate binding and provides insights into the automodification bias of PARP1.
Caldecott, K. W., Aoufouchi, S., Johnson, P. & Shall, S. XRCC1 polypeptide interacts with DNA polymerase-β and possibly poly (ADP-ribose) polymerase, and DNA ligase III is a novel molecular 'nick-sensor' in vitro. Nucleic Acids Res. 24, 4387–4394 (1996).
Langelier, M. F., Planck, J. L., Roy, S. & Pascal, J. M. Structural basis for DNA damage-dependent poly(ADP-ribosyl)ation by human PARP-1. Science 336, 728–732 (2012).
Lilyestrom, W., van der Woerd, M. J., Clark, N. & Luger, K. Structural and biophysical studies of human PARP-1 in complex with damaged DNA. J. Mol. Biol. 395, 983–994 (2010).
Eustermann, S. et al. The DNA-binding domain of human PARP-1 interacts with DNA single-strand breaks as a monomer through its second zinc finger. J. Mol. Biol. 407, 149–170 (2011).
Altmeyer, M., Messner, S., Hassa, P. O., Fey, M. & Hottiger, M. O. 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 (2009).
Kim, M. Y., Mauro, S., Gevry, N., Lis, J. T. & Kraus, W. L. NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1. Cell 119, 803–814 (2004).
D'Amours, D., Desnoyers, S., D'Silva, I. & Poirier, G. G. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem. J. 342, 249–268 (1999).
Kraus, W. L. & Lis, J. T. PARP goes transcription. Cell 113, 677–683 (2003).
Pinnola, A., Naumova, N., Shah, M. & Tulin, A. V. 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, 32511–32519 (2007).
Kotova, E. et al. Drosophila histone H2A variant (H2Av) controls poly(ADP-ribose) polymerase 1 (PARP1) activation in chromatin. Proc. Natl Acad. Sci. USA 108, 6205–6210 (2011).
Petesch, S. J. & Lis, J. T. Rapid, transcription-independent loss of nucleosomes over a large chromatin domain at Hsp70 loci. Cell 134, 74–84 (2008).
Petesch, S. J. & Lis, J. T. Activator-induced spread of Poly(ADP-Ribose) polymerase promotes nucleosome loss at Hsp70. Mol. Cell 45, 64–74 (2012).
Schreiber, V. et al. Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1. J. Biol. Chem. 277, 23028–23036 (2002).
Cohen-Armon, M. et al. DNA-independent PARP-1 activation by phosphorylated ERK2 increases Elk1 activity: a link to histone acetylation. Mol. Cell 25, 297–308 (2007).
Chi, N. W. & Lodish, H. F. Tankyrase is a golgi-associated mitogen-activated protein kinase substrate that interacts with IRAP in GLUT4 vesicles. J. Biol. Chem. 275, 38437–38444 (2000).
Guettler, S. et al. Structural basis and sequence rules for substrate recognition by Tankyrase explain the basis for cherubism disease. Cell 147, 1340–1354 (2011). Provides a detailed structural and functional description of the ankyrin repeat domains of tankyrases and their recognition of the ankyrin repeat recognition sequence. Provides mechanistic insights into how loss of this recognition underlies the human disease cherubism.
Levaot, N. et al. Loss of Tankyrase-mediated destruction of 3BP2 is the underlying pathogenic mechanism of cherubism. Cell 147, 1324–1339 (2011). The authors use mouse models for cherubism, and an elegant series of molecular analyses, to show that the molecular basis for cherubism lies in the misregulation of tankyrase recognition of 3BP2 and 3BP2 PARylation. This is the first human disease to be directly linked to abrogation of PAR-directed ubiquitylation and subsequent target destruction.
Ryu, H. et al. PIASy mediates SUMO-2/3 conjugation of poly(ADP-ribose) polymerase 1 (PARP1) on mitotic chromosomes. J. Biol. Chem. 285, 14415–14423 (2010).
Martin, N. et al. PARP-1 transcriptional activity is regulated by sumoylation upon heat shock. EMBO J. 28, 3534–3548 (2009).
Mao, Z. et al. SIRT6 promotes DNA repair under stress by activating PARP1. Science 332, 1443–1446 (2011). Describes DNA-damage-driven crosstalk between the mono(ADP-ribosyl) transferase SIRT6 and the damage response protein PARP1. Suggests that mono(ADPribosyl)ating enzymes may kick-start PARylation by PARPs by adding the first ADP-ribose unit to target proteins.
Mendoza-Alvarez, H. & Alvarez-Gonzalez, R. Poly(ADP-ribose) polymerase is a catalytic dimer and the automodification reaction is intermolecular. J. Biol. Chem. 268, 22575–22580 (1993).
Leung, A. K. et al. Poly(ADP-ribose) regulates stress responses and microRNA activity in the cytoplasm. Mol. Cell 42, 489–499 (2011). Provides evidence that multiple PARP family members form an integrated stress response network, and that PAR polymers are an integral component of stress granules at the nexus of PARylating enzymes and PAR-binding proteins.
Collier, R. J. Understanding the mode of action of diphtheria toxin: a perspective on progress during the 20th century. Toxicon 39, 1793–1803 (2001).
Asher, G. et al. Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding. Cell 142, 943–953 (2010). Demonstrates that PARP1 is crucial for normal circadian rhythm control by feeding cycles. Provides a clear example of how PARylation promotes the inactivation of a target protein by showing that feeding-driven PARylation of the transcription factor CLOCK inhibits its DNA binding and gene-regulating activities.
Krishnakumar, R. & Kraus, W. L. PARP-1 regulates chromatin structure and transcription through a KDM5B-dependent pathway. Mol. Cell 39, 736–749 (2010).
Abd Elmageed, Z. Y., Naura, A. S., Errami, Y. & Zerfaoui, M. The poly(ADP-ribose) polymerases (PARPs): new roles in intracellular transport. Cell. Signal. 24, 1–8 (2012).
Sala, A. et al. The nucleosome-remodeling ATPase ISWI is regulated by poly-ADP-ribosylation. PLoS Biol. 6, e252 (2008).
Smith, S., Giriat, I., Schmitt, A. & de Lange, T. Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science 282, 1484–1487 (1998).
Wacker, D. A. et al. The DNA binding and catalytic domains of poly(ADP-ribose) polymerase 1 cooperate in the regulation of chromatin structure and transcription. Mol. Cell. Biol. 27, 7475–7485 (2007).
Stilmann, M. et al. A nuclear poly(ADP-ribose)-dependent signalosome confers DNA damage-induced IκB kinase activation. Mol. Cell 36, 365–378 (2009). Describes a PAR-driven signalling mechanism in which PAR-binding is a prerequisite for protein–protein interactions in the DNA damage response.
Ahel, D. et al. Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1. Science 325, 1240–1243 (2009).
Chou, D. M. et al. 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. USA 107, 18475–18480 (2010). Reports the results of a high-throughput screen that identifies a host of proteins that bind to chromatin following DNA-damage induction in a PAR-directed manner. The PAR-directed recruitment of chromatin-modifying complexes, such as Polycomb and NuRD, allows transcription to be repressed in the region of DNA damage.
Li, G. Y. et al. Structure and identification of ADP-ribose recognition motifs of APLF and role in the DNA damage response. Proc. Natl Acad. Sci. USA 107, 9129–9134 (2010).
Ahel, I. et al. Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins. Nature 451, 81–85 (2008).
Masson, M. et al. XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Mol. Cell. Biol. 18, 3563–3571 (1998).
Okano, S., Lan, L., Caldecott, K. W., Mori, T. & Yasui, A. Spatial and temporal cellular responses to single-strand breaks in human cells. Mol. Cell. Biol. 23, 3974–3981 (2003).
Chang, P., Coughlin, M. & Mitchison, T. J. Tankyrase-1 polymerization of poly(ADP-ribose) is required for spindle structure and function. Nature Cell Biol. 7, 1133–1139 (2005).
Chang, P., Coughlin, M. & Mitchison, T. J. Interaction between Poly(ADP-ribose) and NuMA contributes to mitotic spindle pole assembly. Mol. Biol. Cell 20, 4575–4585 (2009).
Chang, P., Jacobson, M. K. & Mitchison, T. J. Poly(ADP-ribose) is required for spindle assembly and structure. Nature 432, 645–649 (2004).
Kotova, E., Jarnik, M. & Tulin, A. V. Poly (ADP-ribose) polymerase 1 is required for protein localization to Cajal body. PLoS Genet. 5, e1000387 (2009).
Aravind, L. The WWE domain: a common interaction module in protein ubiquitination and ADP ribosylation. Trends Biochem. Sci. 26, 273–275 (2001).
Wang, T., Simbulan-Rosenthal, C. M., Smulson, M. E., Chock, P. B. & Yang, D. C. Polyubiquitylation of PARP-1 through ubiquitin K48 is modulated by activated DNA, NAD+, and dipeptides. J. Cell Biochem. 104, 318–328 (2008).
Chang, W., Dynek, J. N. & Smith, S. TRF1 is degraded by ubiquitin-mediated proteolysis after release from telomeres. Genes Dev. 17, 1328–1333 (2003).
Wang, Z. et al. Recognition of the iso-ADP-ribose moiety in poly(ADP-ribose) by WWE domains suggests a general mechanism for poly(ADP-ribosyl)ation-dependent ubiquitination. Genes Dev. 26, 235–240 (2012). Describes the discovery of a fourth PAR-binding module, termed the WWE domain.
Kang, H. C. et al. Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates DNA damage. Proc. Natl Acad. Sci. USA 108, 14103–14108 (2011).
Zhang, Y. et al. RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Nature Cell Biol. 13, 623–629 (2011). References 80 and 81 demonstrate that the PAR-binding protein RNF146 is a PAR-directed E3 ubiquitin ligase, thereby linking PARylation to PARP target protein destruction.
Andrabi, S. A. et al. Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death. Nature Med. 17, 692–699 (2011).
Huang, S. M. et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 461, 614–620 (2009).
Kashima, L. et al. CHFR regulates the mitotic checkpoint by targeting PARP-1 for ubiquitination and degradation. J. Biol. Chem. 287, 12975–12984 (2012).
Bacalini, M. G. et al. Poly(ADP-ribosyl)ation affects stabilization of Che-1 protein in response to DNA damage. DNA Repair (Amst.) 10, 380–389 (2011).
Andrabi, S. A., Dawson, T. M. & Dawson, V. L. Mitochondrial and nuclear cross talk in cell death: parthanatos. Ann. NY Acad. Sci. 1147, 233–241 (2008).
Wang, X., Yang, C., Chai, J., Shi, Y. & Xue, D. Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans. Science 298, 1587–1592 (2002).
Yu, S. W. et al. Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science 297, 259–263 (2002).
Smith, B. C., Hallows, W. C. & Denu, J. M. A continuous microplate assay for sirtuins and nicotinamide-producing enzymes. Anal. Biochem. 394, 101–109 (2009).
Karras, G. I. et al. The macro domain is an ADP-ribose binding module. EMBO J. 24, 1911–1920 (2005).
Kolisek, M., Beck, A., Fleig, A. & Penner, R. Cyclic ADP-ribose and hydrogen peroxide synergize with ADP-ribose in the activation of TRPM2 channels. Mol. Cell 18, 61–69 (2005).
Koh, D. W. et al. Failure to degrade poly(ADP-ribose) causes increased sensitivity to cytotoxicity and early embryonic lethality. Proc. Natl Acad. Sci. USA 101, 17699–17704 (2004).
Mortusewicz, O., Fouquerel, E., Ame, J. C., Leonhardt, H. & Schreiber, V. PARG is recruited to DNA damage sites through poly(ADP-ribose)- and PCNA-dependent mechanisms. Nucleic Acids Res. 39, 5045–5056 (2011).
Frizzell, K. M. et al. 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 (2009).
Gagne, J. P. et al. Proteome-wide identification of poly(ADP-ribose) binding proteins and poly(ADP-ribose)-associated protein complexes. Nucleic Acids Res. 36, 6959–6976 (2008).
Pleschke, J. M., Kleczkowska, H. E., Strohm, M. & Althaus, F. R. Poly(ADP-ribose) binds to specific domains in DNA damage checkpoint proteins. J. Biol. Chem. 275, 40974–40980 (2000).
Huambachano, O., Herrera, F., Rancourt, A. & Satoh, M. S. Double-stranded DNA binding domain of poly(ADP-ribose) polymerase-1 and molecular insight into the regulation of its activity. J. Biol. Chem. 286, 7149–7160 (2011).
Murawska, M., Hassler, M., Renkawitz-Pohl, R., Ladurner, A. & Brehm, A. Stress-induced PARP activation mediates recruitment of Drosophila Mi-2 to promote heat shock gene expression. PLoS Genet. 7, e1002206 (2011).
Eustermann, S. et al. Solution structures of the two PBZ domains from human APLF and their interaction with poly(ADP-ribose). Nature Struct. Mol. Biol. 17, 241–243 (2010).
Oberoi, J. et al. Structural basis of poly(ADP-ribose) recognition by the multizinc binding domain of checkpoint with forkhead-associated and RING domains (CHFR). J. Biol. Chem. 285, 39348–39358 (2010).
Han, W., Li, X. & Fu, X. The macro domain protein family: structure, functions, and their potential therapeutic implications. Mutat. Res. 727, 86–103 (2011).
Kustatscher, G., Hothorn, M., Pugieux, C., Scheffzek, K. & Ladurner, A. G. Splicing regulates NAD metabolite binding to histone macroH2A. Nature Struct. Mol. Biol. 12, 624–625 (2005).
Peterson, F. C. et al. Orphan macrodomain protein (human C6orf130) is an O-acyl-ADP-ribose deacylase: solution structure and catalytic properties. J. Biol. Chem. 286, 35955–35965 (2011).
Chen, D. et al. Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases. J. Biol. Chem. 286, 13261–13271 (2011).
Mehrotra, P. V. et al. DNA repair factor APLF is a histone chaperone. Mol. Cell 41, 46–55 (2011).
Gottschalk, A. J. et al. Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler. Proc. Natl Acad. Sci. USA 106, 13770–13774 (2009).
Specht, K. M. & Shokat, K. M. The emerging power of chemical genetics. Curr. Opin. Cell Biol. 14, 155–159 (2002).
Anders, C. K. et al. Poly(ADP-ribose) polymerase inhibition: “targeted” therapy for triple-negative breast cancer. Clin. Cancer Res. 16, 4702–4710 (2010).
Papeo, G. et al. Poly(ADP-ribose) polymerase inhibition in cancer therapy: are we close to maturity? Expert Opin. Ther. Pat. 19, 1377–1400 (2009).
Pacher, P. & Szabo, C. Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: the therapeutic potential of PARP inhibitors. Cardiovasc. Drug Rev. 25, 235–260 (2007).
Shevalye, H. et al. Poly(ADP-ribose) polymerase (PARP) inhibition counteracts multiple manifestations of kidney disease in long-term streptozotocin-diabetic rat model. Biochem. Pharmacol. 79, 1007–1014 (2010).
Masutani, M., Nakagama, H. & Sugimura, T. Poly(ADP-ribosyl)ation in relation to cancer and autoimmune disease. Cell. Mol. Life Sci. 62, 769–783 (2005).
Mota, R. A. et al. Inhibition of poly(ADP-ribose) polymerase attenuates the severity of acute pancreatitis and associated lung injury. Lab. Invest. 85, 1250–1262 (2005).
Bryant, H. E. et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434, 913–917 (2005).
Farmer, H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917–921 (2005).
Fong, P. C. et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N. Engl. J. Med. 361, 123–134 (2009).
Gelmon, K. A. et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 12, 852–861 (2011).
O'Shaughnessy, J. et al. Iniparib plus chemotherapy i n metastatic triple-negative breast cancer. N. Engl. J. Med. 364, 205–214 (2011).
Guha, M. PARP inhibitors stumble in breast cancer. Nature Biotech. 29, 373–374 (2011).
Patel, A. G., De Lorenzo, S. B., Flatten, K. S., Poirier, G. G. & Kaufmann, S. H. Failure of iniparib to inhibit poly(ADP-ribose) polymerase in vitro. Clin. Cancer Res. 18, 1655–1662 (2012).
Liu, X. et al. Iniparib nonselectively modifies cysteine-containing proteins in tumor cells and is not a bona fide PARP inhibitor. Clin. Cancer Res. 18, 510–523 (2012).
Wahlberg, E. et al. Family-wide chemical profiling and structural analysis of PARP and tankyrase inhibitors. Nature Biotech. 30, 283–288 (2012).
Narwal, M., Venkannagari, H. & Lehtio, L. Structural basis of selective inhibition of human tankyrases. J. Med. Chem. 55, 1360–1367 (2012).
Southan, G. J. & Szabo, C. Poly(ADP-ribose) polymerase inhibitors. Curr. Med. Chem. 10, 321–340 (2003).