Damage-induced ubiquitylation of human RNA polymerase II by the ubiquitin ligase Nedd4, but not Cockayne syndrome proteins or BRCA1.
Mol Cell
; 28(3): 386-97, 2007 Nov 09.
Article
em En
| MEDLINE
| ID: mdl-17996703
ABSTRACT
UV-induced RNA polymerase II (RNAPII) ubiquitylation and degradation are important DNA damage responses, conserved from yeast to man. However, the identity of the human enzymes that mediate these responses has been unclear. Previously, Cockayne syndrome proteins and BRCA1 were implicated in the process. Surprisingly, using a recently developed assay system, we found that these factors are not directly involved in RNAPII ubiquitylation. The defects in RNAPII ubiquitylation observed in CS cells are caused by an indirect mechanism these cells shut down transcription in response to DNA damage, effectively depleting the substrate for ubiquitylation, namely elongating RNAPII. Instead, we identified Nedd4 as an E3 that associates with and ubiquitylates RNAPII in response to UV-induced DNA damage in human cells. Nedd4-dependent RNAPII ubiquitylation could also be reconstituted with highly purified proteins. Together, our results indicate that transcriptional arrest at DNA lesions triggers Nedd4 recruitment and RNAPII ubiquitylation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Dano ao DNA
/
RNA Polimerase II
/
DNA Helicases
/
Proteína BRCA1
/
Enzimas Reparadoras do DNA
/
Ubiquitina-Proteína Ligases
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article