ArticleCurrent biology : CB2015
Tethering of SCF(Dia2) to the Replisome Promotes Efficient Ubiquitylation and Disassembly of the CMG Helicase.
Article in Current biology : CB, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 42 citations in OpenAlex.
- Ubiquitin-proteasome system regulates pro-crossover protein dynamics during meiosis in Caenorhabditis elegans.PLoS biology · 2026Article
- A systematic quantitative approach comprehensively defines domain-specific functional pathways linked to Schizosaccharomyces pombe heterochromatin regulation.Nucleic acids research · 2024Article
- CMG helicase disassembly is essential and driven by two pathways in budding yeast.The EMBO journal · 2024Article
- COSA-1 mediated pro-crossover complex formation promotes meiotic crossing over in C. elegans.Nucleic acids research · 2024Article
- Review
- A systematic quantitative approach comprehensively defines domain-specific functional pathways linked tobioRxiv : the preprint server for biology · 2024Article
- Implications of ubiquitination and the maintenance of replication fork stability in cancer therapy.Bioscience reports · 2023Review
- Cooperative assembly of p97 complexes involved in replication termination.Nature communications · 2022Article
- Repression of essential cell cycle genes increases cellular fitness.PLoS genetics · 2022Article
- Article
- The Effect of Dia2 Protein Deficiency on the Cell Cycle, Cell Size, and Recruitment of Ctf4 Protein inMolecules (Basel, Switzerland) · 2021Article
- Structure of CRL2Lrr1, the E3 ubiquitin ligase that promotes DNA replication termination in vertebrates.Nucleic acids research · 2021Article
- Article
- TIMELESS-TIPIN and UBXN-3 promote replisome disassembly during DNA replication termination in Caenorhabditis elegans.The EMBO journal · 2021Article
- Coordinating DNA Replication and Mitosis through Ubiquitin/SUMO and CDK1.International journal of molecular sciences · 2021Review
- The Fate of Two Unstoppable Trains After Arriving Destination: Replisome Disassembly During DNA Replication Termination.Frontiers in cell and developmental biology · 2021Review
- Article
- Mechanisms of eukaryotic replisome disassembly.Biochemical Society transactions · 2020Review
- In Vitro Reconstitution Defines the Minimal Requirements for Cdc48-Dependent Disassembly of the CMG Helicase in Budding Yeast.Cell reports · 2019Article
- Proteolytic control of genome integrity at the replication fork.DNA repair · 2019Review
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Disassembly of the Cdc45-MCM-GINS (CMG) DNA helicase, which unwinds the parental DNA duplex at eukaryotic replication forks, is the key regulated step during replication termination but is poorly understood. In budding yeast, the F-box protein Dia2 drives ubiquitylation of the CMG helicase at the end of replication, leading to a disassembly pathway that requires the Cdc48 segregase. The substrate-binding domain of Dia2 comprises leucine-rich repeats, but Dia2 also has a TPR domain at its amino terminus that interacts with the Ctf4 and Mrc1 subunits of the replisome progression complex, which assembles around the CMG helicase at replication forks. Previous studies suggested two disparate roles for the TPR domain of Dia2, either mediating replisome-specific degradation of Mrc1 and Ctf4 or else tethering SCF(Dia2) (SCF [Skp1/cullin/F-box protein]) to the replisome to increase its local concentration at replication forks. Here, we show that SCF(Dia2) does not mediate replisome-specific degradation of Mrc1 and Ctf4, either during normal S phase or in response to replication stress. Instead, the tethering of SCF(Dia2) to the replisome progression complex increases the efficiency of ubiquitylation of the Mcm7 subunit of CMG, both in vitro and in vivo. Correspondingly, loss of tethering reduces the efficiency of CMG disassembly in vivo and is synthetic lethal in combination with a disassembly-defective allele of CDC48. Residual ubiquitylation of Mcm7 in dia2-ΔTPR cells is still CMG specific, highlighting the complex regulation of the final stages of chromosome replication, about which much still remains to be learned.
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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.