title: The diverse roles and clinical relevance of PARPs in DNA damage repair: current state of the art.
abstract: Poly(ADP-ribose) polymerase (PARP) catalyzed poly(ADP-ribosyl)ation is one of the earliest post-translational modification of proteins detectable at sites of DNA strand interruptions. The considerable recent progress in the science of PARP in the last decade and the discovery of a PARP superfamily (17 members) has introduced this modification as a key mechanism regulating a wide variety of cellular processes including among others transcription, regulation of chromatin dynamics, telomere homeostasis, differentiation and cell death. However, the most extensive studied and probably the best characterized role is in DNA repair where it plays pivotal roles in the processing and resolution of the damaged DNA. Although much of the focus has been on PARP1 in DNA repair, recent advances highlight the emergence of other DNA-dependent PARPs (i.e. PARP2, PARP3 and possibly Tankyrase) in this process. Here we will summarize the recent insights into the molecular functions of these PARPs in different DNA repair pathways in which they emerge as specific actors. Furthermore, the DNA repair functions of PARP1 have stimulated another area of intense research in the field with the development of potent and selective PARP1 inhibitors to promote genome instability and cell death in tumor cells. Their current use in clinical trials have demonstrated potentiation of antitumoral drugs and cytotoxicity in repair deficient tumor cells.
authors.affiliation: UMR7242-CNRS-Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, Ecole Supérieure de Biotechnologie de Strasbourg, bld. S. Brant, BP10413, 67412 Illkirch, France.
authors.forename: Mike
authors.initials: M
authors.lastname: De Vos
authors.forename: Valérie
authors.initials: V
authors.lastname: Schreiber
authors.forename: Françoise
authors.initials: F
authors.lastname: Dantzer
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D053904:DNA Breaks, Single-Stranded; D004249:DNA Damage; D004260:DNA Repair; D042822:Genomic Instability; D059765:Homologous Recombination; D006801:Humans; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D038501:Tankyrases / Q000378:metabolism; D059505:Telomere Homeostasis
chemical_list: D018797:Cell Cycle Proteins; C499320:PARP1 protein, human; C483041:PARP2 protein, human; C480979:PARP3 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D038501:Tankyrases