ATM induces MacroD2 nuclear export upon DNA damage.

ADP-ribosylation is a dynamic post-translation modification that regulates the early phase of various DNA repair pathways by recruiting repair factors to chromatin. ADP-ribosylation levels are defined by the activities of specific transferases and hydrolases. However, except for the transferase PARP1/ARDT1 little is known about regulation of these enzymes. We found that MacroD2, a mono-ADP-ribosylhydrolase, is exported from the nucleus upon DNA damage, and that this nuclear export is induced by ATM activity. We show that the export is dependent on the phosphorylation of two SQ/TQ motifs, suggesting a novel direct interaction between ATM and ADP-ribosylation. Lastly, we show that MacroD2 nuclear export temporally restricts its recruitment to DNA lesions, which may decrease the net ADP-ribosylhydrolase activity at the site of DNA damage. Together, our results identify a novel feedback regulation between two crucial DNA damage-induced signaling pathways: ADP-ribosylation and ATM activation. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Citation

Barbara Golia, Giuliana Katharina Moeller, Gytis Jankevicius, Andreas Schmidt, Anna Hegele, Julia Preißer, Mai Ly Tran, Axel Imhof, Gyula Timinszky. ATM induces MacroD2 nuclear export upon DNA damage. Nucleic acids research. 2017 Jan 09;45(1):244-254

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PMID: 28069995

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