ArticleNucleic acids research2025
CDK-driven phosphorylation of TRAIP is essential for mitotic replisome disassembly and MiDAS.
Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Mitotic kinase regulation of DNA replication forks.bioRxiv : the preprint server for biology · 2026Article
- Oncogenic SOX9-TRAIP signaling drives gastric cancer progression by mediating the degradation of the CPEB3-mTORC1 tumor suppressor axis.World journal of surgical oncology · 2026Article
- Ubiquitin and SUMO pathways in DNA replication and replication-coupled repair.Critical reviews in biochemistry and molecular biologyReview
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9 authors.
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Abstract
Disassembly of the replication machinery (replisome) from chromatin is an active process driven by two ubiquitin ligases Cul2LRR1 and TRAIP, which both target the Mcm7 subunit of the replicative helicase for ubiquitylation. Uncontrolled unloading of replisomes during S-phase would be disastrous for genome stability and cell viability. On the other hand, replisomes retained on under-replicated DNA in mitosis require removal to allow access and processing of the DNA before cell division. TRAIP ubiquitylates replisomes in mitosis but can also act in specific situations during S-phase. However, we do not know how TRAIP's activity is regulated to stop uncontrolled replisome unloading. Here we show that TRAIP activity towards replisomes is not regulated at the level of interaction with the substrate: it interacts with terminated replisomes in S-phase without ubiquitylation. However, in mitosis, TRAIP is phosphorylated by cyclin-dependent kinases (CDKs) and this phosphorylation is essential for mitotic replisome unloading. CDK phosphorylation of TRAIP stimulates its autoubiquitylation activity and ubiquitylation of replisomes isolated from mitotic chromatin. The phosphorylation of TRAIP is also important in human cells for TRAIP functions during MiDAS. Although essential during mitosis, the CDK-driven phosphorylation of TRAIP is not sufficient to activate uncontrolled unloading of replisomes in S-phase.
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