title: ATM induces MacroD2 nuclear export upon DNA damage.
abstract: 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.
authors.affiliation: Department of Physiological Chemistry, Biomedical Center, Ludwig-Maximilians-Universität München, Planegg-Martinsried 82152, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Golia
authors.affiliation: Department of Physiological Chemistry, Biomedical Center, Ludwig-Maximilians-Universität München, Planegg-Martinsried 82152, Germany.
authors.forename: Giuliana Katharina
authors.initials: GK
authors.lastname: Moeller
authors.affiliation: Department of Physiological Chemistry, Biomedical Center, Ludwig-Maximilians-Universität München, Planegg-Martinsried 82152, Germany.
authors.forename: Gytis
authors.initials: G
authors.lastname: Jankevicius
authors.affiliation: Zentrallabor für Proteinanalytik (Protein Analysis Unit), Ludwig-Maximilians-Universität München, Planegg-Martinsried 82152, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Department of Physiological Chemistry, Biomedical Center, Ludwig-Maximilians-Universität München, Planegg-Martinsried 82152, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Hegele
authors.affiliation: Department of Physiological Chemistry, Biomedical Center, Ludwig-Maximilians-Universität München, Planegg-Martinsried 82152, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Preißer
authors.affiliation: Department of Physiological Chemistry, Biomedical Center, Ludwig-Maximilians-Universität München, Planegg-Martinsried 82152, Germany.
authors.forename: Mai Ly
authors.initials: ML
authors.lastname: Tran
authors.affiliation: Zentrallabor für Proteinanalytik (Protein Analysis Unit), Ludwig-Maximilians-Universität München, Planegg-Martinsried 82152, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Imhof
authors.affiliation: Department of Physiological Chemistry, Biomedical Center, Ludwig-Maximilians-Universität München, Planegg-Martinsried 82152, Germany gyula.timinszky@med.uni-muenchen.de.
authors.forename: Gyula
authors.initials: G
authors.lastname: Timinszky
mesh_terms: D021581:Active Transport, Cell Nucleus; D000244:Adenosine Diphosphate / Q000378:metabolism*; D020816:Amino Acid Motifs; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004249:DNA Damage; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D025461:Feedback, Physiological; D006367:HeLa Cells; D006801:Humans; D006867:Hydrolases / Q000235:genetics* / Q000378:metabolism; D010006:Osteoblasts; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
chemical_list: C523332:MACROD2 protein, human; D000244:Adenosine Diphosphate; D011065:Poly(ADP-ribose) Polymerases; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D006867:Hydrolases; D045643:DNA Repair Enzymes