PARP-2, A Novel Mammalian DNA Damage-dependent Poly(ADP-ribose) Polymerase

doi:10.1074/jbc.274.25.17860

PARP-2, A Novel Mammalian DNA Damage-dependent Poly(ADP-ribose) Polymerase*

From the ^‡UPR 9003 du CNRS, Ecole Supérieure de Biotechnologie de Strasbourg, Boulevard Sébastien Brant, F-67400 Illkirch, France, the ^‖Institut Curie Recherche UMR 147, Rue d’Ulm, F-75248 Paris Cedex, France,^‡Pharmaceuticals Research, BASF AG, D-67056 Ludwigshafen, Germany, and the ^**Institut de Biologie Moléculaire et Cellulaire, UPR du 9021 CNRS, 15 rue RenéDescartes, F-67000 Strasbourg, France

Abstract

Poly(ADP-ribosylation) is a post-translational modification of nuclear proteins in response to DNA damage that activates the base excision repair machinery. Poly(ADP-ribose) polymerase which we will now call PARP-1, has been the only known enzyme of this type for over 30 years. Here, we describe a cDNA encoding a 62-kDa protein that shares considerable homology with the catalytic domain of PARP-1 and also contains a basic DNA-binding domain. We propose to call this enzyme poly(ADP-ribose) polymerase 2 (PARP-2). The PARP-2 gene maps to chromosome 14C1 and 14q11.2 in mouse and human, respectively. Purified recombinant mouse PARP-2 is a damaged DNA-binding protein in vitro and catalyzes the formation of poly(ADP-ribose) polymers in a DNA-dependent manner. PARP-2 displays automodification properties similar to PARP-1. The protein is localized in the nucleusin vivo and may account for the residual poly(ADP-ribose) synthesis observed in PARP-1-deficient cells, treated with alkylating agents or hydrogen peroxide.

Footnotes

↵* This work was supported in part by the Association pour la Recherche Contre le Cancer, Electricité de France, CNRS Grant ACC-SV Radiations ionisantes, Fondation pour la Recherche Médicale, and the Commissariat à l’Energie Atomique.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵§ Contributed equally to the results of this report.
↵¶ Recipient of a postdoctoral fellowship from the Fondation pour la Recherche Médicale.
↵§§ To whom all correspondence should be addressed: UPR 9003 du CNRS, Laboratoire conventionné avec le Commissariat à l’Energie Atomique, Ecole Supérieure de Biotechnologie de Strasbourg, Boulevard Sébastien Brant, F-67400 Illkirch, France. Tel.: 33-388-65-53-68; Fax: 33-388-65-53-52; E-mail:demurcia{at}esbs.u-strasbg.fr.
↵2 M. Kazmaier, personal communication.
↵3 C. Niedergang, J.-C. Amé, V. Schreiber, J. Ménissier-de Murcia, and G. de Murcia, unpublished data.
Abbreviations:

PARP

poly(ADP-ribose) polymerase

MMS

methylmethanesulfonate

EST

expressed sequence tags

FISH

fluorescence in situhybridization

PAGE

polyacrylamide gel electrophoresis

wt

wild type

aa

amino acid(s)

PCR

polymerase chain reaction

bp

base pair(s)

GST

glutathione S-transferase

GFP

green fluorescent protein

DAPI

4,6-diamidino-2-phenylindole
- Received February 1, 1999.
- Revision received April 1, 1999.
The American Society for Biochemistry and Molecular Biology, Inc.