ArticleNucleic acids research2019
Conditional degradation of SDE2 by the Arg/N-End rule pathway regulates stress response at replication forks.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- USP5 acts as a proteolytic switch to control SDE2 function via UBL-directed cleavage.Nature communications · 2026Article
- DEGRONOPEDIA: a web server for proteome-wide inspection of degrons.Nucleic acids research · 2024Article
- Replisome dysfunction upon inducible TIMELESS degradation synergizes with ATR inhibition to trigger replication catastrophe.Nucleic acids research · 2023Article
- Splicing of branchpoint-distant exons is promoted by Cactin, Tls1 and the ubiquitin-fold-activated Sde2.Nucleic acids research · 2022Article
- SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing.Nucleic acids research · 2021Article
- Signaling Pathways Regulated by UBR Box-Containing E3 Ligases.International journal of molecular sciences · 2021Review
- The emerging determinants of replication fork stability.Nucleic acids research · 2021Review
- Review
- The C-degron pathway eliminates mislocalized proteins and products of deubiquitinating enzymes.The EMBO journal · 2021Article
- Roles of SDE2 and TIMELESS at active and stalled DNA replication forks.Molecular & cellular oncology · 2021Article
- SDE2 integrates into the TIMELESS-TIPIN complex to protect stalled replication forks.Nature communications · 2020Article
- Proteome dynamics analysis identifies functional roles of SDE2 and hypoxia in DNA damage response in prostate cancer cells.NAR cancer · 2020Article
- Downregulation of the Arg/N-degron Pathway Sensitizes Cancer Cells to Chemotherapy In Vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Proteolytic control of genome integrity at the replication fork.DNA repair · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Multiple pathways counteract DNA replication stress to prevent genomic instability and tumorigenesis. The recently identified human SDE2 is a genome surveillance protein regulated by PCNA, a DNA clamp and processivity factor at replication forks. Here, we show that SDE2 cleavage after its ubiquitin-like domain generates Lys-SDE2Ct, the C-terminal SDE2 fragment bearing an N-terminal Lys residue. Lys-SDE2Ct constitutes a short-lived physiological substrate of the Arg/N-end rule proteolytic pathway, in which UBR1 and UBR2 ubiquitin ligases mediate the degradation. The Arg/N-end rule and VCP/p97UFD1-NPL4 segregase cooperate to promote phosphorylation-dependent, chromatin-associated Lys-SDE2Ct degradation upon UVC damage. Conversely, cells expressing the degradation-refractory K78V mutant, Val-SDE2Ct, fail to induce RPA phosphorylation and single-stranded DNA formation, leading to defects in PCNA-dependent DNA damage bypass and stalled fork recovery. Together, our study elucidates a previously unappreciated axis connecting the Arg/N-end rule and the p97-mediated proteolysis with the replication stress response, working together to preserve replication fork integrity.
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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.