Abstract
Proteasome-mediated proteolysis provides dynamic spatial and temporal modulation of protein concentration in response to various intrinsic and extrinsic challenges. To gain a better understanding of the role of the proteasome in DNA repair, we systematically monitored the stability of 26 proteins involved in nucleotide excision repair (NER) under normal growth conditions. Among six NER factors found to be regulated by the proteasome, we further delineated the specific pathway involved in the degradation of Rad25, a subunit of TFIIH. We demonstrate that Rad25 turnover requires the ubiquitin-conjugating enzyme Ubc4 and the ubiquitin ligase Ufd4. Interestingly, the deletion of UFD4 specifically suppresses the rad25 mutant defective in transcription. Our results reveal a novel function of the Ufd4 pathway and another tie between the proteasome and NER regulators.
Highlights
The proteolytic regulation of DNA repair factors remains poorly understood
Among six nucleotide excision repair (NER) factors found to be regulated by the proteasome, we further delineated the specific pathway involved in the degradation of Rad[25], a subunit of TFIIH
To elucidate the involvement of the ubiquitin-proteasome system (UPS) in NER, we evaluated the protein stability of 26 known yeast NER factors (Fig. 1) that are appended with MORF or TAP tags and available from Open Biosystems
Summary
Results: Six proteins involved in nucleotide excision repair are found to be degraded by the proteasome. Conclusion: Rad[25] is selected for proteasomal degradation by the Ubc4-Ufd[4] pathway. Significance: Our results provide novel insights into the role of the proteasome in DNA repair. To gain a better understanding of the role of the proteasome in DNA repair, we systematically monitored the stability of 26 proteins involved in nucleotide excision repair (NER) under normal growth conditions. Among six NER factors found to be regulated by the proteasome, we further delineated the specific pathway involved in the degradation of Rad[25], a subunit of TFIIH. Our results reveal a novel function of the Ufd[4] pathway and another tie between the proteasome and NER regulators. The ubiquitin-proteasome system (UPS)[3] regulates a broad range of biological processes, including cell cycle progression, immune response, signal transduction, gene expression, and
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