Year : 2014 ARTD 2 activity is stimulated by RNA

ADP-ribosyltransferases (ARTs) are important enzymes that regulate the genotoxic stress response and the maintenance of genome integrity. ARTD1 (PARP1) and ARTD2 (PARP2) are homologous proteins that modify themselves and target proteins by the addition of monoand poly-ADP-ribose (PAR) moieties. Both enzymes have been described to be involved in the genotoxic stress response. Here, we characterize cellular PAR formation on hydrogen peroxide (H2O2) or N-methyl-N’-methyl-nitro-Nnitrosoguanidine (MNNG) stress, in combination with application of the RNA polymerase I inhibitor Actinomycin D (ActD), known to cause accumulation of short RNA polymerase I-dependent rRNA transcripts. Intriguingly, co-treatment with ActD substantially increased H2O2or MNNG-induced PAR formation. In cells, this enhancement was predominantly mediated by ARTD2 and not ARTD1. In vitro experiments confirmed that ARTD2 is strongly activated by RNA and that the N-terminal SAP domain is important for the binding to RNA. Thus, our findings identify a new activator of ARTD2dependent ADP-ribosylation, which has important implications for the future analysis of the biological role of ARTD2 in the nucleus. DOI: https://doi.org/10.1093/nar/gku131 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-100141 Published Version Originally published at: Léger, Karolin; Bär, Dominik; Savić, Nataša; Santoro, Raffaella; Hottiger, Michael O (2014). ARTD2 activity is stimulated by RNA. Nucleic Acids Research, 42(8):5072-5082. DOI: https://doi.org/10.1093/nar/gku131 ARTD2 activity is stimulated by RNA Karolin Léger, Dominik Bär, Nataša Savić, Raffaella Santoro and Michael O. Hottiger* Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland and Life Science Zurich Graduate School, University of Zurich, 8057 Zurich, Switzerland Received April 29, 2013; Revised January 20, 2014; Accepted January 22, 2014