Ubiquitin-SUMO circuitry controls activated fanconi anemia ID complex dosage in response to DNA damage.
Mol Cell
; 57(1): 150-64, 2015 Jan 08.
Article
em En
| MEDLINE
| ID: mdl-25557546
ABSTRACT
We show that central components of the Fanconi anemia (FA) DNA repair pathway, the tumor suppressor proteins FANCI and FANCD2 (the ID complex), are SUMOylated in response to replication fork stalling. The ID complex is SUMOylated in a manner that depends on the ATR kinase, the FA ubiquitin ligase core complex, and the SUMO E3 ligases PIAS1/PIAS4 and is antagonized by the SUMO protease SENP6. SUMOylation of the ID complex drives substrate selectivity by triggering its polyubiquitylation by the SUMO-targeted ubiquitin ligase RNF4 to promote its removal from sites of DNA damage via the DVC1-p97 ubiquitin segregase complex. Deregulation of ID complex SUMOylation compromises cell survival following replication stress. Our results uncover a regulatory role for SUMOylation in the FA pathway, and we propose that ubiquitin-SUMO signaling circuitry is a mechanism that contributes to the balance of activated ID complex dosage at sites of DNA damage.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Cisteína Endopeptidases
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Proteínas Nucleares
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Ubiquitina
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Proteínas de Grupos de Complementação da Anemia de Fanconi
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Proteína do Grupo de Complementação D2 da Anemia de Fanconi
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article