Evidence map›Paper›PMID 40637231›Full record

ArticleNucleic acids research2025

CDK-driven phosphorylation of TRAIP is essential for mitotic replisome disassembly and MiDAS.

Divyasree Poovathumkadavil, Alicja Reynolds-Winczura, Aggeliki Skagia, Paolo Passaretti, Martina Muste Sadurni, Georgia Kingsley, Alexander Leitner, Marco Saponaro, Agnieszka Gambus

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Mitotic kinase regulation of DNA replication forks.bioRxiv : the preprint server for biology · 2026
    Article
  2. Article
  3. Ubiquitin and SUMO pathways in DNA replication and replication-coupled repair.Critical reviews in biochemistry and molecular biology
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Divyasree PoovathumkadavilDepartment of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
Alicja Reynolds-WinczuraDepartment of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
Aggeliki SkagiaDepartment of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
Paolo PassarettiDepartment of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
Martina Muste SadurniDepartment of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
Georgia KingsleyDepartment of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
Alexander LeitnerDepartment of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, 8093, Switzerland.ORCID 0000-0003-4126-0725
Marco SaponaroDepartment of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham, B15 2TT, United Kingdom.ORCID 0000-0002-9302-2553
Agnieszka GambusDepartment of Cancer and Genomic Sciences, Birmingham Centre for Genome Biology, University of Birmingham, Birmingham, B15 2TT, United Kingdom.ORCID 0000-0002-4648-0332

Funding

Biotechnology and Biological Sciences Research Council BB/T001860/1Biotechnology and Biological Sciences Research Council BB/Y002458/1Biotechnology and Biological Sciences Research Council BB/Y006232/1MRCWellcome Trust 215510/Z/19/Z
6 · The paper itself

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.

Indexed as

Cyclin-Dependent KinasesDNA ReplicationMitosisUbiquitin-Protein LigasesCell Cycle ProteinsChromatinHeLa CellsHumansMinichromosome Maintenance Complex Component 7PhosphorylationS PhaseUbiquitinationCell Cycle ProteinsChromatinCyclin-Dependent KinasesMCM7 protein, humanMinichromosome Maintenance Complex Component 7TICRR protein, humanUbiquitin-Protein Ligases

Identifiers

PMID40637231
PMCPMC12242765

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Registered trials

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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.