SET7/9-dependent methylation of ARTD1 at K508 stimulates poly-ADP-ribose formation after oxidative stress. Issue 10 (October 2013)

• Record Type: Journal Article
• Authors: Kassner, Ingrid; Andersson, Anneli; Fey, Monika; Tomas, Martin; Ferrando-May, Elisa; Hottiger, Michael O.
• Is Part Of: Open biology. Volume 3:Issue 10(2013)
• Publication Date: 2013-10
• Subjects: ADP-ribosylation -- lysine methylation -- PARP-1 -- protein regulation -- SET7/9; Biology -- Periodicals; 570
• DOI: 10.1098/rsob.120173
• Languages: English
• ISSNs: 2046-2441

Abstract

Abstract : ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1, formerly PARP1) is localized in the nucleus, where it ADP-ribosylates specific target proteins. The post-translational modification (PTM) with a single ADP-ribose unit or with polymeric ADP-ribose (PAR) chains regulates protein function as well as protein–protein interactions and is implicated in many biological processes and diseases. SET7/9 (Setd7, KMT7) is a protein methyltransferase that catalyses lysine monomethylation of histones, but also methylates many non-histone target proteins such as p53 or DNMT1. Here, we identify ARTD1 as a new SET7/9 target protein that is methylated at K508 in vitro and in vivo . ARTD1 auto-modification inhibits its methylation by SET7/9, while auto-poly-ADP-ribosylation is not impaired by prior methylation of ARTD1. Moreover, ARTD1 methylation by SET7/9 enhances the synthesis of PAR upon oxidative stress in vivo . Furthermore, laser irradiation-induced PAR formation and ARTD1 recruitment to sites of DNA damage in a SET7/9-dependent manner. Together, these results reveal a novel mechanism for the regulation of cellular ARTD1 activity by SET7/9 to assure efficient PAR formation upon cellular stress.