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ARTD2 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 mono- and poly-ADP-ribose (PAR) moieties. Bo...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005644/ https://www.ncbi.nlm.nih.gov/pubmed/24510188 http://dx.doi.org/10.1093/nar/gku131 |
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author | Léger, Karolin Bär, Dominik Savić, Nataša Santoro, Raffaella Hottiger, Michael O. |
author_facet | Léger, Karolin Bär, Dominik Savić, Nataša Santoro, Raffaella Hottiger, Michael O. |
author_sort | Léger, Karolin |
collection | PubMed |
description | 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 mono- and 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 (H(2)O(2)) or N-methyl-N′-methyl-nitro-N-nitrosoguanidine (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 H(2)O(2)- or 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 ARTD2-dependent ADP-ribosylation, which has important implications for the future analysis of the biological role of ARTD2 in the nucleus. |
format | Online Article Text |
id | pubmed-4005644 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40056442014-05-01 ARTD2 activity is stimulated by RNA Léger, Karolin Bär, Dominik Savić, Nataša Santoro, Raffaella Hottiger, Michael O. Nucleic Acids Res Molecular Biology 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 mono- and 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 (H(2)O(2)) or N-methyl-N′-methyl-nitro-N-nitrosoguanidine (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 H(2)O(2)- or 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 ARTD2-dependent ADP-ribosylation, which has important implications for the future analysis of the biological role of ARTD2 in the nucleus. Oxford University Press 2014-04 2014-02-08 /pmc/articles/PMC4005644/ /pubmed/24510188 http://dx.doi.org/10.1093/nar/gku131 Text en © The Author(s) 2014. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Molecular Biology Léger, Karolin Bär, Dominik Savić, Nataša Santoro, Raffaella Hottiger, Michael O. ARTD2 activity is stimulated by RNA |
title | ARTD2 activity is stimulated by RNA |
title_full | ARTD2 activity is stimulated by RNA |
title_fullStr | ARTD2 activity is stimulated by RNA |
title_full_unstemmed | ARTD2 activity is stimulated by RNA |
title_short | ARTD2 activity is stimulated by RNA |
title_sort | artd2 activity is stimulated by rna |
topic | Molecular Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005644/ https://www.ncbi.nlm.nih.gov/pubmed/24510188 http://dx.doi.org/10.1093/nar/gku131 |
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