ArticleCell2013
Proteasome-mediated processing of Def1, a critical step in the cellular response to transcription stress.
Article in Cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 89 citations in OpenAlex.
- Degradation factor 1, Def1, regulates mRNA translation and decay through Ccr4-Not-dependent ubiquitylation of the ribosome.RNA (New York, N.Y.) · 2026Article
- Transcriptional PBR cycles at pericentromeric repeats cause gross chromosomal rearrangements through Rad52-dependent ADR-loop formation.Nucleic acids research · 2026Article
- Degradation factor 1, Def1, regulates mRNA translation and decay through Ccr4-Not-dependent ubiquitylation of the ribosome.bioRxiv : the preprint server for biology · 2025Article
- Review
- Proteasomal processing of the viral replicase ORF1 facilitates HEV-induced liver fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Transcription-replication conflicts drive R-loop-dependent nucleosome eviction and require DOT1L activity for transcription recovery.Nucleic acids research · 2025Article
- VPS28 regulates triglyceride synthesis via ubiquitination in bovine mammary epithelial cells.Scientific reports · 2024Article
- Characterization of BioID tagging systems in budding yeast and exploring the interactome of the Ccr4-Not complex.G3 (Bethesda, Md.) · 2024Article
- Post-translational modification-dependent oligomerization switch in regulation of global transcription and DNA damage repair during genotoxic stress.Nature communications · 2024Article
- New roles for elongation factors in RNA polymerase II ubiquitylation and degradation.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Review
- Ubx5-Cdc48 assists the protease Wss1 at DNA-protein crosslink sites in yeast.The EMBO journal · 2023Article
- The Ubiquitin-like Proteins ofBiomolecules · 2023Review
- RNAPII Degradation Factor Def1 Is Required for Development, Stress Response, and Full Virulence ofJournal of fungi (Basel, Switzerland) · 2023Article
- RNA polymerase II transcription attenuation at the yeast DNA repair gene DEF1 is biologically significant and dependent on the Hrp1 RNA-recognition motif.G3 (Bethesda, Md.) · 2023Article
- Regulation of RNA Polymerase I Stability and Function.Cancers · 2022Review
- ATM-mediated ELL phosphorylation enhances its self-association through increased EAF1 interaction and inhibits global transcription during genotoxic stress.Nucleic acids research · 2022Article
- Yeast Smy2 and its human homologs GIGYF1 and -2 regulate Cdc48/VCP function during transcription stress.Cell reports · 2022Article
- The Paf1 complex is required for RNA polymerase II removal in response to DNA damage.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Proteasome-dependent truncation of the negative heterochromatin regulator Epe1 mediates antifungal resistance.Nature structural & molecular biology · 2022Article
- Dppa3 facilitates self-renewal of embryonic stem cells by stabilization of pluripotent factors.Stem cell research & therapy · 2022Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
DNA damage triggers polyubiquitylation and degradation of the largest subunit of RNA polymerase II (RNAPII), a "mechanism of last resort" employed during transcription stress. In yeast, this process is dependent on Def1 through a previously unresolved mechanism. Here, we report that Def1 becomes activated through ubiquitylation- and proteasome-dependent processing. Def1 processing results in the removal of a domain promoting cytoplasmic localization, resulting in nuclear accumulation of the clipped protein. Nuclear Def1 then binds RNAPII, utilizing a ubiquitin-binding domain to recruit the Elongin-Cullin E3 ligase complex via a ubiquitin-homology domain in the Ela1 protein. This facilitates polyubiquitylation of Rpb1, triggering its proteasome-mediated degradation. Together, these results outline the multistep mechanism of Rpb1 polyubiquitylation triggered by transcription stress and uncover the key role played by Def1 as a facilitator of Elongin-Cullin ubiquitin ligase function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.