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A family of macrodomain proteins reverses cellular mono-ADP-ribosylation

ADP-ribosylation is a reversible post-translational modification with wide-ranging biological functions in all kingdoms of life. A variety of enzymes use NAD(+) to transfer either single or multiple ADP-ribose (ADPr) moieties onto distinct amino acid substrates, often in response to DNA damage or ot...

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Detalles Bibliográficos
Autores principales: Jankevicius, Gytis, Hassler, Markus, Golia, Barbara, Rybin, Vladimir, Zacharias, Martin, Timinszky, Gyula, Ladurner, Andreas G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097781/
https://www.ncbi.nlm.nih.gov/pubmed/23474712
http://dx.doi.org/10.1038/nsmb.2523
Descripción
Sumario:ADP-ribosylation is a reversible post-translational modification with wide-ranging biological functions in all kingdoms of life. A variety of enzymes use NAD(+) to transfer either single or multiple ADP-ribose (ADPr) moieties onto distinct amino acid substrates, often in response to DNA damage or other stresses. Poly-ADPr-glycohydrolase readily reverses poly-ADP-ribosylation induced by the DNA-damage sensor PARP1 and other enzymes, but it does not remove the most proximal ADPr linked to the target amino acid. Searches for enzymes capable of fully reversing cellular mono-ADP-ribosylation back to the unmodified state have proved elusive, which leaves a gap in the understanding of this modification. Here, we identify a family of macrodomain enzymes present in viruses, yeast and animals that reverse cellular ADP-ribosylation by acting on mono-ADP-ribosylated substrates. Our discoveries establish the complete reversibility of PARP-catalyzed cellular ADP-ribosylation as a regulatory modification. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nsmb.2523) contains supplementary material, which is available to authorized users.