The deubiquitinase OTUD5 regulates Ku80 stability and non-homologous end joining.
Cell Mol Life Sci
; 76(19): 3861-3873, 2019 Oct.
Article
en En
| MEDLINE
| ID: mdl-30980112
ABSTRACT
The ability of cells to repair DNA double-strand breaks (DSBs) is important for maintaining genome stability and eliminating oncogenic DNA lesions. Two distinct and complementary pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are employed by mammalian cells to repair DNA DSBs. Each pathway is tightly controlled in response to increased DSBs. The Ku heterodimer has been shown to play a regulatory role in NHEJ repair. Ku80 ubiquitination contributes to the selection of a DSB repair pathway by causing the removal of Ku heterodimers from DSB sites. However, whether Ku80 deubiquitination also plays a role in regulating DSB repair is unknown. To address this question, we performed a comprehensive study of the deubiquitinase specific for Ku80, and our study showed that the deubiquitinase OTUD5 serves as an important regulator of NHEJ repair by increasing the stability of Ku80. Further studies revealed that OTUD5 depletion impaired NHEJ repair, and hence reduced overall DSB repair. Furthermore, OTUD5-depleted cells displayed excess end resection; as a result, HR repair was facilitated by OTUD5 depletion during the S/G2 phase. In summary, our study demonstrates that OTUD5 is a specific deubiquitinase for Ku80 and establishes OTUD5 as an important and positive regulator of NHEJ repair.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Endopeptidasas
/
Reparación del ADN por Unión de Extremidades
/
Autoantígeno Ku
Límite:
Humans
Idioma:
En
Revista:
Cell Mol Life Sci
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2019
Tipo del documento:
Article
País de afiliación:
China