Distinct functions of the ubiquitin-proteasome pathway influence nucleotide excision repair

Thomas G. Gillette, Shirong Yu, Zheng Zhou, Raymond Waters, Stephen Albert Johnston, Simon H. Reed

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2529-2538
Number of pages10
JournalEMBO Journal
Volume25
Issue number11
DOIs
StatePublished - Jul 7 2006

Fingerprint

Proteasome Endopeptidase Complex
Ubiquitin
DNA Repair
Repair
Nucleotides
Ultraviolet radiation
Radiation
Ubiquitin-Protein Ligases
Ubiquitination
Proteins
Cullin Proteins
Ubiquitinated Proteins
Ligases
Degradation
DNA

Keywords

  • DNA repair
  • NER
  • Proteasome
  • Ubiquitin
  • Yeast

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Gillette, T. G., Yu, S., Zhou, Z., Waters, R., Johnston, S. A., & Reed, S. H. (2006). Distinct functions of the ubiquitin-proteasome pathway influence nucleotide excision repair. EMBO Journal, 25(11), 2529-2538. https://doi.org/10.1038/sj.emboj.7601120

Distinct functions of the ubiquitin-proteasome pathway influence nucleotide excision repair. / Gillette, Thomas G.; Yu, Shirong; Zhou, Zheng; Waters, Raymond; Johnston, Stephen Albert; Reed, Simon H.

In: EMBO Journal, Vol. 25, No. 11, 07.07.2006, p. 2529-2538.

Research output: Contribution to journalArticle

Gillette, TG, Yu, S, Zhou, Z, Waters, R, Johnston, SA & Reed, SH 2006, 'Distinct functions of the ubiquitin-proteasome pathway influence nucleotide excision repair', EMBO Journal, vol. 25, no. 11, pp. 2529-2538. https://doi.org/10.1038/sj.emboj.7601120
Gillette, Thomas G. ; Yu, Shirong ; Zhou, Zheng ; Waters, Raymond ; Johnston, Stephen Albert ; Reed, Simon H. / Distinct functions of the ubiquitin-proteasome pathway influence nucleotide excision repair. In: EMBO Journal. 2006 ; Vol. 25, No. 11. pp. 2529-2538.
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