PARP-2, a novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase

Poly(ADP-ribosylation) is a post-translational modification of nuclear prot eins in response to DNA damage that activates the base excision repair mach inery. 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 c DNA encoding a 62-kDa protein that shares considerable homology with the ca talytic domain of PARP-1 and also contains a basic DNA-binding domain. We p ropose 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, respectivel y, Purified recombinant mouse PARP-2 is a damaged DNA-binding protein in vi tro and catalyzes the formation of poly(ADP-ribose) polymers in a DNA-depen dent manner. PARP-2 displays automodification properties similar to PARP-1. The protein is localized in the nucleus in vivo and may account for the re sidual poly(ADP-ribose) synthesis observed in PARP-1-deficient cells, treat ed with alkylating agents or hydrogen peroxide.