title: Poly(ADP-ribose) polymerase 3 (PARP3), a newcomer in cellular response to DNA damage and mitotic progression.
abstract: The ADP ribosyl transferase [poly(ADP-ribose) polymerase] ARTD3(PARP3) is a newly characterized member of the ARTD(PARP) family that catalyzes the reaction of ADP ribosylation, a key posttranslational modification of proteins involved in different signaling pathways from DNA damage to energy metabolism and organismal memory. This enzyme shares high structural similarities with the DNA repair enzymes PARP1 and PARP2 and accordingly has been found to catalyse poly(ADP ribose) synthesis. However, relatively little is known about its in vivo cellular properties. By combining biochemical studies with the generation and characterization of loss-of-function human and mouse models, we describe PARP3 as a newcomer in genome integrity and mitotic progression. We report a particular role of PARP3 in cellular response to double-strand breaks, most likely in concert with PARP1. We identify PARP3 as a critical player in the stabilization of the mitotic spindle and in telomere integrity notably by associating and regulating the mitotic components NuMA and tankyrase 1. Both functions open stimulating prospects for specifically targeting PARP3 in cancer therapy.
authors.affiliation: Research Institute of the Biotechnology School of Strasbourg, UMR7242, Ecole Supérieure de Biotechnologie de Strasbourg, 67412 Illkirch, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Boehler
authors.forename: Laurent R
authors.initials: LR
authors.lastname: Gauthier
authors.forename: Oliver
authors.initials: O
authors.lastname: Mortusewicz
authors.forename: Denis S
authors.initials: DS
authors.lastname: Biard
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Saliou
authors.forename: Anne
authors.initials: A
authors.lastname: Bresson
authors.forename: Sarah
authors.initials: S
authors.lastname: Sanglier-Cianferani
authors.forename: Susan
authors.initials: S
authors.lastname: Smith
authors.forename: Valérie
authors.initials: V
authors.lastname: Schreiber
authors.forename: François
authors.initials: F
authors.lastname: Boussin
authors.forename: Françoise
authors.initials: F
authors.lastname: Dantzer
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D003114:Colony-Forming Units Assay; D020552:Comet Assay; D053903:DNA Breaks, Double-Stranded; D017931:DNA Primers / Q000235:genetics; D019084:Fluorescent Antibody Technique, Indirect; D042822:Genomic Instability / Q000235:genetics* / Q000502:physiology; D006801:Humans; D047468:Immunoprecipitation; D017404:In Situ Hybridization, Fluorescence; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D018715:Microscopy, Video; D008938:Mitosis / Q000235:genetics* / Q000502:physiology; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency / Q000378:metabolism*; D008941:Spindle Apparatus / Q000502:physiology*; D038501:Tankyrases / Q000378:metabolism
chemical_list: D000244:Adenosine Diphosphate; D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D017931:DNA Primers; D034521:Nuclear Matrix-Associated Proteins; D011065:Poly(ADP-ribose) Polymerases; D038501:Tankyrases; C050045:NUMA1 protein, human; C480979:PARP3 protein, human; C418109:TNKS protein, human