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Poly(ADP-ribosylation) and genomic stability

Publication: Biochemistry and Cell Biology
June 2005

Abstract

Poly(ADP-ribose) polymerases (PARPs) catalyze the synthesis of ADP-ribose polymers and attach them to specific target proteins. To date, 6 members of this protein family in humans have been characterized. The best-known PARP, PARP-1, is located within the nucleus and has a major function in DNA repair but also in the execution of cell death pathways. Other PARP enzymes appear to carry out highly specific functions. Most prominently, the tankyrases modify telomere-binding proteins and thereby regulate telomere maintenance. Since only a single enzyme, poly(ADP-ribose) glycohydrolase (PARG), has been identified, which degrades poly(ADP-ribose), it is expected that this protein has important roles in PARP-mediated regulatory processes. This review summarizes recent observations indicating that poly(ADP-ribosylation) represents a major mechanism to regulate genomic stability both when DNA is damaged by exogenous agents and during cell division.Key words: DNA repair, PARP, PARG, tankyrase, telomere maintenance.

Résumé

Les poly(ADP-ribose) polymérases (PARPs) catalysent la synthèse de polymères d'ADP-ribose et les attachent à des protéines cibles spécifiques. À ce jour, six membres de cette famille de protéines ont été caractérisés chez l'humain. La PARP la mieux connue, PARP-1, est localisée au noyau et joue un rôle majeur non seulement dans la réparation d'ADN, mais aussi dans l'exécution de différents sentiers menant à la mort cellulaire. D'autres PARP exercent des fonctions hautement spécifiques. Parmi les plus remarquables, les tankyrases modifient les protéines liant les télomères, régulant de ce fait le maintien des télomères. Puisque l'on n'a identifié qu'une seule enzyme responsable de la dégradation des poly(ADP-ribose), la poly(ADP-ribose) glycohydrolase (PARG), on s'attend à ce que cette protéine joue des rôles importants dans les processus régulateurs dépendants de la PARP. Cette revue résume les observations récentes indiquant que la poly(ADP-ribosylation) représente un mécanisme majeur de régulation de la stabilité génomique, tant lorsque l'ADN est endommagé par des agents exogènes que lors de la division cellulaire.Mots clés : réparation de l'ADN, PARP, PARG, tankyrase, entretien des télomères.[Traduit par la Rédaction]

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cover image Biochemistry and Cell Biology
Biochemistry and Cell Biology
Volume 83Number 3June 2005
Pages: 263 - 269

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Version of record online: 24 January 2011

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