HERC2-USP20 axis regulates DNA damage checkpoint through Claspin.
Nucleic Acids Res
; 42(21): 13110-21, 2014 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-25355518
ABSTRACT
The DNA damage response triggers cell-cycle checkpoints, DNA repair and apoptosis using multiple post-translational modifications as molecular switches. However, how ubiquitination regulates ATR signaling in response to replication stress and single-strand break is still unclear. Here, we identified the deubiquitination enzyme (DUB) USP20 as a pivotal regulator of ATR-related DDR pathway. Through screening a panel of DUBs, we identified USP20 as critical for replication stress response. USP20 is phosphorylated by ATR, resulting in disassociation of the E3 ubiquitin ligase HERC2 from USP20 and USP20 stabilization. USP20 in turn deubiquitinates and stabilizes Claspin and enhances the activation of ATR-Chk1 signaling. These findings reveal USP20 to be a novel regulator of ATR-dependent DNA damage signaling.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Factores de Intercambio de Guanina Nucleótido
/
Ubiquitina Tiolesterasa
/
Proteínas Adaptadoras Transductoras de Señales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2014
Tipo del documento:
Article
País de afiliación:
China