Poly(ADP-ribosyl)ation Reactions in the Regulation of Nuclear Functions

Overview

Journal Biochem J

Specialty Biochemistry

Date 1999 Aug 24

PMID 10455009

Citations 743

Authors

D DAmours

S Desnoyers

I DSilva

G G Poirier

Affiliations

Soon will be listed here.

Abstract

Poly(ADP-ribosyl)ation is a post-translational modification of proteins. During this process, molecules of ADP-ribose are added successively on to acceptor proteins to form branched polymers. This modification is transient but very extensive in vivo, as polymer chains can reach more than 200 units on protein acceptors. The existence of the poly(ADP-ribose) polymer was first reported nearly 40 years ago. Since then, the importance of poly(ADP-ribose) synthesis has been established in many cellular processes. However, a clear and unified picture of the physiological role of poly(ADP-ribosyl)ation still remains to be established. The total dependence of poly(ADP-ribose) synthesis on DNA strand breaks strongly suggests that this post-translational modification is involved in the metabolism of nucleic acids. This view is also supported by the identification of direct protein-protein interactions involving poly(ADP-ribose) polymerase (113 kDa PARP), an enzyme catalysing the formation of poly(ADP-ribose), and key effectors of DNA repair, replication and transcription reactions. The presence of PARP in these multiprotein complexes, in addition to the actual poly(ADP-ribosyl)ation of some components of these complexes, clearly supports an important role for poly(ADP-ribosyl)ation reactions in DNA transactions. Accordingly, inhibition of poly(ADP-ribose) synthesis by any of several approaches and the analysis of PARP-deficient cells has revealed that the absence of poly(ADP-ribosyl)ation strongly affects DNA metabolism, most notably DNA repair. The recent identification of new poly(ADP-ribosyl)ating enzymes with distinct (non-standard) structures in eukaryotes and archaea has revealed a novel level of complexity in the regulation of poly(ADP-ribose) metabolism.

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References

Ruf A, de Murcia G, Schulz G . Inhibitor and NAD+ binding to poly(ADP-ribose) polymerase as derived from crystal structures and homology modeling. Biochemistry. 1998; 37(11):3893-900. DOI: 10.1021/bi972383s. View

Nie J, Sakamoto S, Song D, Qu Z, Ota K, Taniguchi T . Interaction of Oct-1 and automodification domain of poly(ADP-ribose) synthetase. FEBS Lett. 1998; 424(1-2):27-32. DOI: 10.1016/s0014-5793(98)00131-8. View

Thraves P, Kasid U, Smulson M . Selective isolation of domains of chromatin proximal to both carcinogen-induced DNA damage and poly-adenosine diphosphate-ribosylation. Cancer Res. 1985; 45(1):386-91. View

Huletsky A, Niedergang C, Frechette A, Aubin R, Gaudreau A, Poirier G . Sequential ADP-ribosylation pattern of nucleosomal histones. ADP-ribosylation of nucleosomal histones. Eur J Biochem. 1985; 146(2):277-85. DOI: 10.1111/j.1432-1033.1985.tb08650.x. View

Lonn U, Lonn S . Accumulation of 10-kilobase DNA replication intermediates in cells treated with 3-aminobenzamide. Proc Natl Acad Sci U S A. 1985; 82(1):104-8. PMC: 396980. DOI: 10.1073/pnas.82.1.104. View

Oleinick N, Evans H . Poly(ADP-ribose) and the response of cells to ionizing radiation. Radiat Res. 1985; 101(1):29-46. View

Tanuma S, Yagi T, Johnson G . Endogenous ADP ribosylation of high mobility group proteins 1 and 2 and histone H1 following DNA damage in intact cells. Arch Biochem Biophys. 1985; 237(1):38-42. DOI: 10.1016/0003-9861(85)90251-6. View

Rawling J . TFIIF, a basal eukaryotic transcription factor, is a substrate for poly(ADP-ribosyl)ation. Biochem J. 1997; 324 ( Pt 1):249-53. PMC: 1218424. DOI: 10.1042/bj3240249. View

Eguchi Y, Shimizu S, Tsujimoto Y . Intracellular ATP levels determine cell death fate by apoptosis or necrosis. Cancer Res. 1997; 57(10):1835-40. View

10.

Masson M, Mattei M, de Murcia G, Niedergang C . Poly(ADP-ribose) polymerase interacts with a novel human ubiquitin conjugating enzyme: hUbc9. Gene. 1997; 190(2):287-96. DOI: 10.1016/s0378-1119(97)00015-2. View

11.

de Murcia J, Niedergang C, Trucco C, Ricoul M, Dutrillaux B, Mark M . Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. Proc Natl Acad Sci U S A. 1997; 94(14):7303-7. PMC: 23816. DOI: 10.1073/pnas.94.14.7303. View

12.

Weinfeld M, Chaudhry M, DAmours D, Pelletier J, Poirier G, Povirk L . Interaction of DNA-dependent protein kinase and poly(ADP-ribose) polymerase with radiation-induced DNA strand breaks. Radiat Res. 1997; 148(1):22-8. View

13.

Agarwal M, Agarwal A, Taylor W, Wang Z, Wagner E, Stark G . Defective induction but normal activation and function of p53 in mouse cells lacking poly-ADP-ribose polymerase. Oncogene. 1997; 15(9):1035-41. DOI: 10.1038/sj.onc.1201274. View

14.

Wang Z, Stingl L, Morrison C, JANTSCH M, Los M, Schulze-Osthoff K . PARP is important for genomic stability but dispensable in apoptosis. Genes Dev. 1997; 11(18):2347-58. PMC: 316515. DOI: 10.1101/gad.11.18.2347. View

15.

Vaziri H, WEST M, Allsopp R, Davison T, Wu Y, Arrowsmith C . ATM-dependent telomere loss in aging human diploid fibroblasts and DNA damage lead to the post-translational activation of p53 protein involving poly(ADP-ribose) polymerase. EMBO J. 1997; 16(19):6018-33. PMC: 1170232. DOI: 10.1093/emboj/16.19.6018. View

16.

Eliasson M, Sampei K, Mandir A, Hurn P, Traystman R, Bao J . Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia. Nat Med. 1997; 3(10):1089-95. DOI: 10.1038/nm1097-1089. View

17.

Oei S, Griesenbeck J, Schweiger M, Babich V, Kropotov A, Tomilin N . Interaction of the transcription factor YY1 with human poly(ADP-ribosyl) transferase. Biochem Biophys Res Commun. 1997; 240(1):108-11. DOI: 10.1006/bbrc.1997.7621. View

18.

Morrison C, Smith G, Stingl L, Jackson S, Wagner E, Wang Z . Genetic interaction between PARP and DNA-PK in V(D)J recombination and tumorigenesis. Nat Genet. 1997; 17(4):479-82. DOI: 10.1038/ng1297-479. View

19.

Althaus F . Poly(ADP-ribose) catabolism in mammalian cells exposed to DNA-damaging agents. Mutat Res. 1989; 218(2):67-74. DOI: 10.1016/0921-8777(89)90012-8. View

20.

Lefebvre P, Laval F . Potentiation of N-methyl-N'-nitro-N-nitrosoguanidine-induced O6-methylguanine-DNA-methyltransferase activity in a rat hepatoma cell line by poly (ADP-ribose) synthesis inhibitors. Biochem Biophys Res Commun. 1989; 163(1):599-604. DOI: 10.1016/0006-291x(89)92179-7. View