ATM induces MacroD2 nuclear export upon DNA damage.
Nucleic Acids Res
; 45(1): 244-254, 2017 Jan 09.
Article
em En
| MEDLINE
| ID: mdl-28069995
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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Difosfato de Adenosina
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Processamento de Proteína Pós-Traducional
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Poli(ADP-Ribose) Polimerases
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Enzimas Reparadoras do DNA
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Proteínas Mutadas de Ataxia Telangiectasia
/
Hidrolases
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Alemanha