Distinct functions of the ubiquitin-proteasome pathway influence nucleotide excision repair.
EMBO J
; 25(11): 2529-38, 2006 Jun 07.
Article
en En
| MEDLINE
| ID: mdl-16675952
ABSTRACT
The Rad23/Rad4 nucleotide excision repair (NER) protein complex functions at an early stage of the NER reaction, possibly promoting the recognition of damaged DNA. Here we show that Rad4 protein is ubiquitinated and degraded in response to ultraviolet (UV) radiation, and identify a novel cullin-based E3 ubiquitin ligase required for this process. We also show that this novel ubiquitin ligase is required for optimal NER. Our results demonstrate that optimal NER correlates with the ubiquitination of Rad4 following UV radiation, but not its subsequent degradation. Furthermore, we show that the ubiquitin-proteasome pathway (UPP) regulates NER via two distinct mechanisms. The first occurs independently of de novo protein synthesis, and requires Rad23 and a nonproteolytic function of the 19S regulatory complex of the 26S proteasome. The second requires de novo protein synthesis, and relies on the activity of the newly identified E3 ubiquitin ligase. These studies reveal that, following UV radiation, NER is mediated by nonproteolytic activities of the UPP, via the ubiquitin-like domain of Rad23 and UV radiation-induced ubiquitination of Rad4.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Saccharomyces cerevisiae
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Ubiquitina
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Complejo de la Endopetidasa Proteasomal
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Proteínas de Unión al ADN
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Reparación del ADN
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
EMBO J
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos