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Gene Review

PARP1  -  poly (ADP-ribose) polymerase 1

Homo sapiens

Synonyms: ADP-ribosyltransferase diphtheria toxin-like 1, ADPRT, ADPRT 1, ADPRT1, ARTD1, ...
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Disease relevance of PARP1

  • We conclude that increased NF-kappaB prosurvival signaling is a frequent mechanism by which B-precursor ALL tumors develop apoptotic resistance to IR and that PARP1 inhibition may improve the DNA damage response of these leukemias [1].
  • Drugs that specifically up-regulate PARP activity may lead to the disappearance of latent KSHV [2].
  • Tankyrase (TNKS) is a telomere-associated poly-ADP ribose polymerase (PARP) that has been implicated along with several telomere repeat binding factors in the regulation of Epstein-Barr virus origin of plasmid replication (OriP) [3].
  • Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP [4].
  • Additional mutations occurring during cancer progression may be a culprit, although the exact cause for the resistance of BRCA1-/- breast cancer cells to PARP-1 inhibitors remains elusive [5].

Psychiatry related information on PARP1


High impact information on PARP1

  • The NAD+-dependent activities of PARP-1 are reversed by PARG, a poly(ADP-ribose) glycohydrolase, and are inhibited by ATP [7].
  • PARP-1 is the most abundantly expressed member of a family of proteins that catalyze the transfer of ADP-ribose units from NAD+ to target proteins [7].
  • Here, by the use of two different techniques, we show that mice lacking PARP display telomere shortening compared with wild-type mice [8].
  • Telomeres are the natural termini of chromosomes and are, therefore, potential targets of PARP [8].
  • Furthermore, cytogenetic analysis of mouse embryonic fibroblasts reveals that lack of PARP is associated with severe chromosomal instability, characterized by increased frequencies of chromosome fusions and aneuploidy [8].

Chemical compound and disease context of PARP1


Biological context of PARP1


Anatomical context of PARP1


Associations of PARP1 with chemical compounds


Physical interactions of PARP1

  • Furthermore, PARP-1 binding to NACP-Rep1 specifically reduced the transcriptional activity of the SNCA promoter/enhancer in luciferase reporter assays [17].
  • XRCC1 interacts with PARP by its central region (amino acids 301 to 402), which contains a BRCT (BRCA1 C terminus) module, a widespread motif in DNA repair and DNA damage-responsive cell cycle checkpoint proteins [21].
  • These results indicate that the WRN/PARP-1 complex plays a key role in the cellular response to oxidative stress and alkylating agents, suggesting a role for these proteins in the base excision DNA repair pathway [23].
  • PARP-1 also resides for part of the cell cycle in the centrosome and interacts with hPARP-3 [26].
  • Moreover, we found that poly (ADP-ribose) polymerase-1 (PARP-1) is also co-immunoprecipitated with APTX [27].

Enzymatic interactions of PARP1

  • Furthermore, both nucleolin and cleaved PARP-1 were detected in the culture medium of cells undergoing apoptosis, associated with particles of a size consistent with apoptotic bodies [28].
  • METHODS: The effect of IL-6 on apoptosis induced by androgen deprivation in LNCaP cells was examined by cell death ELISA and Western blot using cleaved poly (ADP-ribose) polymerase (PARP) and caspase-9, as well as Bcl-xL and phosphorylated Bad [29].
  • DZA induced a specific cleavage of poly ADP-ribose polymerase (PARP) and an activation of the cysteine protease caspase-3/CPP32 which is known to cleave PARP [30].
  • Purified wild-type PARP-1 catalyzed the poly(ADP-ribosyl) of full-length p53 in vitro [31].

Regulatory relationships of PARP1

  • Hence, inhibition of endogenous PARP-1 function suppresses the transactivation function of p53 in response to ionizing radiation [32].
  • Conversely, PARP-1 enhanced the DNase activity of DFF40 in the absence of NAD(+) [24].
  • We show that unmodified PARP-1 inhibited both WRN exonuclease and helicase activities, and to our knowledge is the only known WRN protein partner that inactivates both of the WRN's catalytic activities suggesting a biologically significant regulation [33].
  • We found that these 53BP2 proteins are located predominantly in the cytoplasm and induce apoptosis as demonstrated by cleavage of poly ADP ribose polymerase (PARP) and annexin V staining [34].
  • Human PARP expressed in E. coli showed a similar effect on pRB-phosphorylation activity of cdk2 [35].

Other interactions of PARP1

  • The association of different NACP-Rep1 alleles with PD may be mediated, in part, by the effect of PARP-1, as well as other factors, on SNCA expression [17].
  • We have identified a physical association between PARP and the base excision repair (BER) protein XRCC1 (X-ray repair cross-complementing 1) in the Saccharomyces cerevisiae system, which was further confirmed to exist in mammalian cells [21].
  • After cellular stress, PARP-1 itself becomes activated, but the poly(ADP-ribosyl)ation of other cellular proteins is severely impaired in WS cells [23].
  • Twenty-one of 40 ALL tumors responded normally to IR, exhibiting accumulation of p53 and p21 proteins and cleavage of caspases 3, 7, and 9 and of PARP1 [1].
  • Another PARP-type enzyme, tankyrase, is involved in the regulation of telomere elongation [14].

Analytical, diagnostic and therapeutic context of PARP1


  1. Apoptotic resistance to ionizing radiation in pediatric B-precursor acute lymphoblastic leukemia frequently involves increased NF-kappaB survival pathway signaling. Weston, V.J., Austen, B., Wei, W., Marston, E., Alvi, A., Lawson, S., Darbyshire, P.J., Griffiths, M., Hill, F., Mann, J.R., Moss, P.A., Taylor, A.M., Stankovic, T. Blood (2004) [Pubmed]
  2. Poly(ADP-ribose) polymerase 1 binds to Kaposi's sarcoma-associated herpesvirus (KSHV) terminal repeat sequence and modulates KSHV replication in latency. Ohsaki, E., Ueda, K., Sakakibara, S., Do, E., Yada, K., Yamanishi, K. J. Virol. (2004) [Pubmed]
  3. Inhibition of Epstein-Barr virus OriP function by tankyrase, a telomere-associated poly-ADP ribose polymerase that binds and modifies EBNA1. Deng, Z., Atanasiu, C., Zhao, K., Marmorstein, R., Sbodio, J.I., Chi, N.W., Lieberman, P.M. J. Virol. (2005) [Pubmed]
  4. Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP. Mantena, S.K., Sharma, S.D., Katiyar, S.K. Carcinogenesis (2006) [Pubmed]
  5. PARP-1 inhibitors: are they the long-sought genetically specific drugs for BRCA1/2-associated breast cancers? De Soto, J.A., Deng, C.X. International journal of medical sciences [electronic resource]. (2006) [Pubmed]
  6. Discovery of bioactive small-molecule inhibitor of poly adp-ribose polymerase: implications for energy-deficient cells. Altmann, S.M., Muryshev, A., Fossale, E., Maxwell, M.M., Norflus, F.N., Fox, J., Hersch, S.M., Young, A.B., MacDonald, M.E., Abagyan, R., Kazantsev, A.G. Chem. Biol. (2006) [Pubmed]
  7. NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1. Kim, M.Y., Mauro, S., Gévry, N., Lis, J.T., Kraus, W.L. Cell (2004) [Pubmed]
  8. Functions of poly(ADP-ribose) polymerase in controlling telomere length and chromosomal stability. d'Adda di Fagagna, F., Hande, M.P., Tong, W.M., Lansdorp, P.M., Wang, Z.Q., Jackson, S.P. Nat. Genet. (1999) [Pubmed]
  9. Poly(ADP-ribose) polymerase-1 and apoptosis inducing factor in neurotoxicity. Yu, S.W., Wang, H., Dawson, T.M., Dawson, V.L. Neurobiol. Dis. (2003) [Pubmed]
  10. Poly(ADP-ribosyl)ation enzyme-1 as a target for neuroprotection in acute central nervous system injury. Skaper, S.D. Current drug targets. CNS and neurological disorders. (2003) [Pubmed]
  11. Baculovirus P35 inhibits the glucocorticoid-mediated pathway of cell death. Robertson, N.M., Zangrilli, J., Fernandes-Alnemri, T., Friesen, P.D., Litwack, G., Alnemri, E.S. Cancer Res. (1997) [Pubmed]
  12. Tumor apoptosis induced by ruthenium(II)-ketoconazole is enhanced in nonsusceptible carcinoma by monoclonal antibody to EGF receptor. Strasberg Rieber, M., Anzellotti, A., Sánchez-Delgado, R.A., Rieber, M. Int. J. Cancer (2004) [Pubmed]
  13. Silibinin causes cell cycle arrest and apoptosis in human bladder transitional cell carcinoma cells by regulating CDKI-CDK-cyclin cascade, and caspase 3 and PARP cleavages. Tyagi, A., Agarwal, C., Harrison, G., Glode, L.M., Agarwal, R. Carcinogenesis (2004) [Pubmed]
  14. A cellular survival switch: poly(ADP-ribosyl)ation stimulates DNA repair and silences transcription. Ziegler, M., Oei, S.L. Bioessays (2001) [Pubmed]
  15. Tankyrase-1 overexpression reduces genotoxin-induced cell death by inhibiting PARP1. Yeh, T.Y., Sbodio, J.I., Nguyen, M.T., Meyer, T.N., Lee, R.M., Chi, N.W. Mol. Cell. Biochem. (2005) [Pubmed]
  16. The role of DNA damage response proteins at telomeres-an "integrative" model. Slijepcevic, P. DNA Repair (Amst.) (2006) [Pubmed]
  17. Regulation of alpha-synuclein expression by poly (ADP ribose) polymerase-1 (PARP-1) binding to the NACP-Rep1 polymorphic site upstream of the SNCA gene. Chiba-Falek, O., Kowalak, J.A., Smulson, M.E., Nussbaum, R.L. Am. J. Hum. Genet. (2005) [Pubmed]
  18. Efficient deletion of normal Brca2-deficient intestinal epithelium by poly(ADP-ribose) polymerase inhibition models potential prophylactic therapy. Hay, T., Jenkins, H., Sansom, O.J., Martin, N.M., Smith, G.C., Clarke, A.R. Cancer Res. (2005) [Pubmed]
  19. TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, causes rapid induction of cell death upon overexpression. Kaminker, P.G., Kim, S.H., Taylor, R.D., Zebarjadian, Y., Funk, W.D., Morin, G.B., Yaswen, P., Campisi, J. J. Biol. Chem. (2001) [Pubmed]
  20. Cooperation of the Cockayne syndrome group B protein and poly(ADP-ribose) polymerase 1 in the response to oxidative stress. Thorslund, T., von Kobbe, C., Harrigan, J.A., Indig, F.E., Christiansen, M., Stevnsner, T., Bohr, V.A. Mol. Cell. Biol. (2005) [Pubmed]
  21. XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Masson, M., Niedergang, C., Schreiber, V., Muller, S., Menissier-de Murcia, J., de Murcia, G. Mol. Cell. Biol. (1998) [Pubmed]
  22. Poly(ADP-ribose) reactivates stalled DNA topoisomerase I and Induces DNA strand break resealing. Malanga, M., Althaus, F.R. J. Biol. Chem. (2004) [Pubmed]
  23. Central role for the Werner syndrome protein/poly(ADP-ribose) polymerase 1 complex in the poly(ADP-ribosyl)ation pathway after DNA damage. von Kobbe, C., Harrigan, J.A., May, A., Opresko, P.L., Dawut, L., Cheng, W.H., Bohr, V.A. Mol. Cell. Biol. (2003) [Pubmed]
  24. Modulation of DNA fragmentation factor 40 nuclease activity by poly(ADP-ribose) polymerase-1. West, J.D., Ji, C., Marnett, L.J. J. Biol. Chem. (2005) [Pubmed]
  25. Deadly conversations: nuclear-mitochondrial cross-talk. Dawson, V.L., Dawson, T.M. J. Bioenerg. Biomembr. (2004) [Pubmed]
  26. PARP-3 localizes preferentially to the daughter centriole and interferes with the G1/S cell cycle progression. Augustin, A., Spenlehauer, C., Dumond, H., Ménissier-De Murcia, J., Piel, M., Schmit, A.C., Apiou, F., Vonesch, J.L., Kock, M., Bornens, M., De Murcia, G. J. Cell. Sci. (2003) [Pubmed]
  27. The FHA domain of aprataxin interacts with the C-terminal region of XRCC1. Date, H., Igarashi, S., Sano, Y., Takahashi, T., Takahashi, T., Takano, H., Tsuji, S., Nishizawa, M., Onodera, O. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  28. Apoptosis in leukemia cells is accompanied by alterations in the levels and localization of nucleolin. Mi, Y., Thomas, S.D., Xu, X., Casson, L.K., Miller, D.M., Bates, P.J. J. Biol. Chem. (2003) [Pubmed]
  29. Interleukin-6 protects LNCaP cells from apoptosis induced by androgen deprivation through the Stat3 pathway. Lee, S.O., Lou, W., Johnson, C.S., Trump, D.L., Gao, A.C. Prostate (2004) [Pubmed]
  30. Induction of apoptosis in human leukemia cells by 3-deazaadenosine is mediated by caspase-3-like activity. Kim, H.S., Jeong, S.Y., Lee, J.H., Kim, B.E., Kim, J.W., Jeong, S.W., Kim, I.K. Exp. Mol. Med. (2000) [Pubmed]
  31. Poly(ADP-ribosyl)ation of p53 in vitro and in vivo modulates binding to its DNA consensus sequence. Simbulan-Rosenthal, C.M., Rosenthal, D.S., Luo, R.B., Samara, R., Jung, M., Dritschilo, A., Spoonde, A., Smulson, M.E. Neoplasia (2001) [Pubmed]
  32. Poly(ADP-ribose) polymerase-1 is a positive regulator of the p53-mediated G1 arrest response following ionizing radiation. Wieler, S., Gagné, J.P., Vaziri, H., Poirier, G.G., Benchimol, S. J. Biol. Chem. (2003) [Pubmed]
  33. Poly(ADP-ribose) polymerase 1 regulates both the exonuclease and helicase activities of the Werner syndrome protein. von Kobbe, C., Harrigan, J.A., Schreiber, V., Stiegler, P., Piotrowski, J., Dawut, L., Bohr, V.A. Nucleic Acids Res. (2004) [Pubmed]
  34. 53BP2 induces apoptosis through the mitochondrial death pathway. Kobayashi, S., Kajino, S., Takahashi, N., Kanazawa, S., Imai, K., Hibi, Y., Ohara, H., Itoh, M., Okamoto, T. Genes Cells (2005) [Pubmed]
  35. Function of poly(ADP-ribose) polymerase in response to DNA damage: gene-disruption study in mice. Masutani, M., Nozaki, T., Nishiyama, E., Shimokawa, T., Tachi, Y., Suzuki, H., Nakagama, H., Wakabayashi, K., Sugimura, T. Mol. Cell. Biochem. (1999) [Pubmed]
  36. Gadd45alpha does not modulate the carboplatin or 5-fluorouracil-induced apoptosis in human papillomavirus-positive cells. Singh, S., Upadhyay, A.K., Ajay, A.K., Bhat, M.K. J. Cell. Biochem. (2007) [Pubmed]
  37. Human nuclear NAD+ ADP-ribosyltransferase: localization of the gene on chromosome 1q41-q42 and expression of an active human enzyme in Escherichia coli. Herzog, H., Zabel, B.U., Schneider, R., Auer, B., Hirsch-Kauffmann, M., Schweiger, M. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  38. Regulation of poly(ADP-ribose) polymerase-1 by DNA structure-specific binding. Lonskaya, I., Potaman, V.N., Shlyakhtenko, L.S., Oussatcheva, E.A., Lyubchenko, Y.L., Soldatenkov, V.A. J. Biol. Chem. (2005) [Pubmed]
  39. Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells. Gupta, S., Afaq, F., Mukhtar, H. Oncogene (2002) [Pubmed]
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