ArticleEMBO reports2024
Combination of AID2 and BromoTag expands the utility of degron-based protein knockdowns.
Article in EMBO reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed.
- Nuclear compartmentalization at the G1/S transition plays a key role in DNA replication control.Nature communications · 2026Article
- Deciphering resistance mechanisms to auxin-inducible protein degradation in mammalian cells.The Journal of biological chemistry · 2026Article
- The benchmarking and application of tag-degraders in vivo to validate therapeutic targets.Nature communications · 2026Article
- BromoCatch: a self-labelling tag platform for protein modification and live cell imaging.Nature communications · 2026Article
- Nucleosome interaction of the CPC secures centromeric chromatin integrity and chromosome segregation fidelity.The EMBO journal · 2025Article
- Aurora-A Promotes Cell-Cycle Progression From Quiescence Through Primary Cilia Disassembly.Cancer science · 2025Article
- Deciphering acquired resistance mechanisms to sustained auxin-inducible protein degradation in cells and mice.bioRxiv : the preprint server for biology · 2025Article
- Temporal control of human DNA replication licensing by CDK4/6-RB signalling and chemical genetics.Nature communications · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Acute protein knockdown is a powerful approach to dissecting protein function in dynamic cellular processes. We previously reported an improved auxin-inducible degron system, AID2, but recently noted that its ability to induce degradation of some essential replication factors, such as ORC1 and CDC6, was not enough to induce lethality. Here, we present combinational degron technologies to control two proteins or enhance target depletion. For this purpose, we initially compare PROTAC-based degrons, dTAG and BromoTag, with AID2 to reveal their key features and then demonstrate control of cohesin and condensin with AID2 and BromoTag, respectively. We develop a double-degron system with AID2 and BromoTag to enhance target depletion and accelerate depletion kinetics and demonstrate that both ORC1 and CDC6 are pivotal for MCM loading. Finally, we show that co-depletion of ORC1 and CDC6 by the double-degron system completely suppresses DNA replication, and the cells enter mitosis with single-chromatid chromosomes, indicating that DNA replication is uncoupled from cell cycle control. Our combinational degron technologies will expand the application scope for functional analyses.
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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.