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 transferases and hydrolases. Little is known about regulation of these enzymes except for that of the transferase ARTD1/PARP1. Among the hydrolases, MacroD2 contains a unique C-terminal region, which may regulate the enzymatic activity carried out by the N-terminal macrodomain. Our study shows that MacroD2 is exported from the nucleus upon DNA damage, and that this nuclear export is induced by ATM activity. In the MacroD2 C-terminal unstructured region we find two SQ/TQ motifs that are necessary for this regulation, arguing for a direct interaction with ATM. This study also shows that MacroD2 nuclear export restricts MacroD2 recruitment to the DNA damage site on the temporal scale, suggesting that the regulation of location determines a regulation of enzymatic activity.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Osteosarcoma

SUBMITTER: Andreas Schmidt  

LAB HEAD: Axel Imhof

PROVIDER: PXD003712 | Pride | 2016-10-12

REPOSITORIES: Pride