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. 2002 Nov 15;368(Pt 1):263–271. doi: 10.1042/BJ20020669

The genes pme-1 and pme-2 encode two poly(ADP-ribose) polymerases in Caenorhabditis elegans.

Steve N Gagnon 1, Michael O Hengartner 1, Serge Desnoyers 1
PMCID: PMC1222961  PMID: 12145714

Abstract

Poly(ADP-ribose) polymerases (PARPs) are an expanding, well-conserved family of enzymes found in many metazoan species, including plants. The enzyme catalyses poly(ADP-ribosyl)ation, a post-translational modification that is important in DNA repair and programmed cell death. In the present study, we report the finding of an endogenous source of poly(ADP-ribosyl)ation in total extracts of the nematode Caenorhabditis elegans. Two cDNAs encoding highly similar proteins to human PARP-1 (huPARP-1) and huPARP-2 are described, and we propose to name the corresponding enzymes poly(ADP-ribose) metabolism enzyme 1 (PME-1) and PME-2 respectively. PME-1 (108 kDa) shares 31% identity with huPARP-1 and has an overall structure similar to other PARP-1 subfamily members. It contains sequences having considerable similarity to zinc-finger motifs I and II, as well as with the catalytic domain of huPARP-1. PME-2 (61 kDa) has structural similarities with the catalytic domain of PARPs in general and shares 24% identity with huPARP-2. Recombinant PME-1 and PME-2 display PARP activity, which may partially account for the similar activity found in the worm. A partial duplication of the pme-1 gene with pseudogene-like features was found in the nematode genome. Messenger RNA for pme-1 are 5'-tagged with splice leader 1, whereas those for pme - 2 are tagged with splice leader 2, suggesting an operon-like expression for pme - 2. The expression pattern of pme-1 and pme-2 is also developmentally regulated. Together, these results show that PARP-1 and -2 are conserved in evolution and must have important functions in multicellular organisms. We propose using C. elegans as a model to understand better the functions of these enzymes.

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Selected References

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  1. Altschul S. F., Madden T. L., Schäffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389–3402. doi: 10.1093/nar/25.17.3389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ame J. C., Schreiber V., Fraulob V., Dolle P., de Murcia G., Niedergang C. P. A bidirectional promoter connects the poly(ADP-ribose) polymerase 2 (PARP-2) gene to the gene for RNase P RNA. structure and expression of the mouse PARP-2 gene. J Biol Chem. 2000 Dec 22;276(14):11092–11099. doi: 10.1074/jbc.M007870200. [DOI] [PubMed] [Google Scholar]
  3. Amé J. C., Rolli V., Schreiber V., Niedergang C., Apiou F., Decker P., Muller S., Höger T., Ménissier-de Murcia J., de Murcia G. PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase. J Biol Chem. 1999 Jun 18;274(25):17860–17868. doi: 10.1074/jbc.274.25.17860. [DOI] [PubMed] [Google Scholar]
  4. Berghammer H., Ebner M., Marksteiner R., Auer B. pADPRT-2: a novel mammalian polymerizing(ADP-ribosyl)transferase gene related to truncated pADPRT homologues in plants and Caenorhabditis elegans. FEBS Lett. 1999 Apr 23;449(2-3):259–263. doi: 10.1016/s0014-5793(99)00448-2. [DOI] [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  6. Braun S. A., Panzeter P. L., Collinge M. A., Althaus F. R. Endoglycosidic cleavage of branched polymers by poly(ADP-ribose) glycohydrolase. Eur J Biochem. 1994 Mar 1;220(2):369–375. doi: 10.1111/j.1432-1033.1994.tb18633.x. [DOI] [PubMed] [Google Scholar]
  7. Brochu G., Duchaine C., Thibeault L., Lagueux J., Shah G. M., Poirier G. G. Mode of action of poly(ADP-ribose) glycohydrolase. Biochim Biophys Acta. 1994 Oct 18;1219(2):342–350. doi: 10.1016/0167-4781(94)90058-2. [DOI] [PubMed] [Google Scholar]
  8. Cherney B. W., McBride O. W., Chen D. F., Alkhatib H., Bhatia K., Hensley P., Smulson M. E. cDNA sequence, protein structure, and chromosomal location of the human gene for poly(ADP-ribose) polymerase. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8370–8374. doi: 10.1073/pnas.84.23.8370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. D'Amours D., Desnoyers S., D'Silva I., Poirier G. G. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J. 1999 Sep 1;342(Pt 2):249–268. [PMC free article] [PubMed] [Google Scholar]
  10. Davidovic L., Vodenicharov M., Affar E. B., Poirier G. G. Importance of poly(ADP-ribose) glycohydrolase in the control of poly(ADP-ribose) metabolism. Exp Cell Res. 2001 Aug 1;268(1):7–13. doi: 10.1006/excr.2001.5263. [DOI] [PubMed] [Google Scholar]
  11. Desnoyers S., Shah G. M., Brochu G., Poirier G. G. Erasable blot of poly(ADP-ribose) polymerase. Anal Biochem. 1994 May 1;218(2):470–473. doi: 10.1006/abio.1994.1212. [DOI] [PubMed] [Google Scholar]
  12. Hengartner M. O., Horvitz H. R. C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell. 1994 Feb 25;76(4):665–676. doi: 10.1016/0092-8674(94)90506-1. [DOI] [PubMed] [Google Scholar]
  13. Johansson M. A human poly(ADP-ribose) polymerase gene family (ADPRTL): cDNA cloning of two novel poly(ADP-ribose) polymerase homologues. Genomics. 1999 May 1;57(3):442–445. doi: 10.1006/geno.1999.5799. [DOI] [PubMed] [Google Scholar]
  14. Kickhoefer V. A., Siva A. C., Kedersha N. L., Inman E. M., Ruland C., Streuli M., Rome L. H. The 193-kD vault protein, VPARP, is a novel poly(ADP-ribose) polymerase. J Cell Biol. 1999 Sep 6;146(5):917–928. doi: 10.1083/jcb.146.5.917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kofler B., Wallraff E., Herzog H., Schneider R., Auer B., Schweiger M. Purification and characterization of NAD+:ADP-ribosyltransferase (polymerizing) from Dictyostelium discoideum. Biochem J. 1993 Jul 1;293(Pt 1):275–281. doi: 10.1042/bj2930275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lepiniec L., Babiychuk E., Kushnir S., Van Montagu M., Inzé D. Characterization of an Arabidopsis thaliana cDNA homologue to animal poly(ADP-ribose) polymerase. FEBS Lett. 1995 May 8;364(2):103–108. doi: 10.1016/0014-5793(95)00335-7. [DOI] [PubMed] [Google Scholar]
  17. Lin W., Amé J. C., Aboul-Ela N., Jacobson E. L., Jacobson M. K. Isolation and characterization of the cDNA encoding bovine poly(ADP-ribose) glycohydrolase. J Biol Chem. 1997 May 2;272(18):11895–11901. doi: 10.1074/jbc.272.18.11895. [DOI] [PubMed] [Google Scholar]
  18. Lyons R. J., Deane R., Lynch D. K., Ye Z. S., Sanderson G. M., Eyre H. J., Sutherland G. R., Daly R. J. Identification of a novel human tankyrase through its interaction with the adaptor protein Grb14. J Biol Chem. 2001 Feb 22;276(20):17172–17180. doi: 10.1074/jbc.M009756200. [DOI] [PubMed] [Google Scholar]
  19. Ma Q., Baldwin K. T., Renzelli A. J., McDaniel A., Dong L. TCDD-inducible poly(ADP-ribose) polymerase: a novel response to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biochem Biophys Res Commun. 2001 Nov 30;289(2):499–506. doi: 10.1006/bbrc.2001.5987. [DOI] [PubMed] [Google Scholar]
  20. Miwa M., Saikawa N., Yamaizumi Z., Nishimura S., Sugimura T. 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. Proc Natl Acad Sci U S A. 1979 Feb;76(2):595–599. doi: 10.1073/pnas.76.2.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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. 1974 Jun 10;249(11):3475–3482. [PubMed] [Google Scholar]
  22. Ménard L., Poirier G. G. Rapid assay of poly(ADP-ribose) glycohydrolase. Biochem Cell Biol. 1987 Jul;65(7):668–673. doi: 10.1139/o87-088. [DOI] [PubMed] [Google Scholar]
  23. Okayama H., Honda M., Hayaishi O. Novel enzyme from rat liver that cleaves an ADP-ribosyl histone linkage. Proc Natl Acad Sci U S A. 1978 May;75(5):2254–2257. doi: 10.1073/pnas.75.5.2254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Panzeter P. L., Realini C. A., Althaus F. R. Noncovalent interactions of poly(adenosine diphosphate ribose) with histones. Biochemistry. 1992 Feb 11;31(5):1379–1385. doi: 10.1021/bi00120a014. [DOI] [PubMed] [Google Scholar]
  25. 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. 1998 Apr 24;278(1):57–65. doi: 10.1006/jmbi.1998.1673. [DOI] [PubMed] [Google Scholar]
  26. Sallmann F. R., Vodenicharov M. D., Wang Z. Q., Poirier G. G. Characterization of sPARP-1. An alternative product of PARP-1 gene with poly(ADP-ribose) polymerase activity independent of DNA strand breaks. J Biol Chem. 2000 May 19;275(20):15504–15511. doi: 10.1074/jbc.275.20.15504. [DOI] [PubMed] [Google Scholar]
  27. Shah G. M., Poirier D., Duchaine C., Brochu G., Desnoyers S., Lagueux J., Verreault A., Hoflack J. C., Kirkland J. B., Poirier G. G. Methods for biochemical study of poly(ADP-ribose) metabolism in vitro and in vivo. Anal Biochem. 1995 May 1;227(1):1–13. doi: 10.1006/abio.1995.1245. [DOI] [PubMed] [Google Scholar]
  28. Shall S., de Murcia G. Poly(ADP-ribose) polymerase-1: what have we learned from the deficient mouse model? Mutat Res. 2000 Jun 30;460(1):1–15. doi: 10.1016/s0921-8777(00)00016-1. [DOI] [PubMed] [Google Scholar]
  29. Smith S., Giriat I., Schmitt A., de Lange T. Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science. 1998 Nov 20;282(5393):1484–1487. doi: 10.1126/science.282.5393.1484. [DOI] [PubMed] [Google Scholar]
  30. Smith S. The world according to PARP. Trends Biochem Sci. 2001 Mar;26(3):174–179. doi: 10.1016/s0968-0004(00)01780-1. [DOI] [PubMed] [Google Scholar]
  31. Wielckens K., Bredehorst R., Hilz H. Quantification of protein-bound ADP-ribosyl and (ADP-ribosyl)n residues. Methods Enzymol. 1984;106:472–482. doi: 10.1016/0076-6879(84)06051-1. [DOI] [PubMed] [Google Scholar]
  32. de Murcia G., Ménissier de Murcia J. Poly(ADP-ribose) polymerase: a molecular nick-sensor. Trends Biochem Sci. 1994 Apr;19(4):172–176. doi: 10.1016/0968-0004(94)90280-1. [DOI] [PubMed] [Google Scholar]

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