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

作者：Jean‐Christophe Amé, Véronique Rolli, Valérie Schreiber, Claude Niedergang, Françoise Apiou, Patrice Decker, Sylviane Muller, Thomas H. Höger, Josiane Ménissier‐de Murcia, Gilbert de MURCIA · 发表于：Journal of Biological Chemistry · 年份：1999 · DOI：10.1074/jbc.274.25.17860 · 被引用次数：757 · 研究领域：PARP inhibition in cancer therapy、DNA Repair Mechanisms、Toxin Mechanisms and Immunotoxins

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 nucleus in vivo and may account for the residual poly(ADP-ribose) synthesis observed in PARP-1-deficient cells, treated with alkylating agents or hydrogen peroxide.