Evidence map›Paper›PMID 30008317›Full record

ArticleMolecular cell2018

DNA Replication Determines Timing of Mitosis by Restricting CDK1 and PLK1 Activation.

Bennie Lemmens, Nadia Hegarat, Karen Akopyan, Joan Sala-Gaston, Jiri Bartek, Helfrid Hochegger, Arne Lindqvist

Open access · hybridAbstract read
In one paragraph

Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
4.8field-weighted citation impact, top 4% of its field
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

87 citing papers in PubMed, 134 citations in OpenAlex.

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  7. ATR kinase inhibitors induce mitochondrial fission in CD8bioRxiv : the preprint server for biology · 2026
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  13. GSK461364 Inhibits NLRP3 Inflammasome by Targeting NEK7 Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
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27 more citing papers are in PubMed but not listed here.

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

7 authors at 4 institutions in 3 countries.

Bennie LemmensDepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden; Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet and Science for Life Laboratory, Stockholm, Sweden.
Nadia HegaratGenome Damage and Stability Centre, University of Sussex, Brighton, UK.
Karen AkopyanDepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Joan Sala-GastonDepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Jiri BartekDivision of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet and Science for Life Laboratory, Stockholm, Sweden; Danish Cancer Society Research Center, Copenhagen, Denmark.
Helfrid HocheggerGenome Damage and Stability Centre, University of Sussex, Brighton, UK. Electronic address: h.hochegger@sussex.ac.uk.
Arne LindqvistDepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. Electronic address: arne.lindqvist@ki.se.
Karolinska Institutet · SEUniversity of Sussex · GBDanish Cancer Society · DKScience for Life Laboratory · SE

Funding

Biotechnology and Biological Sciences Research Council BB/M00354X/1Cancer Research UK C28206/A14499
6 · The paper itself

Abstract

To maintain genome stability, cells need to replicate their DNA before dividing. Upon completion of bulk DNA synthesis, the mitotic kinases CDK1 and PLK1 become active and drive entry into mitosis. Here, we have tested the hypothesis that DNA replication determines the timing of mitotic kinase activation. Using an optimized double-degron system, together with kinase inhibitors to enforce tight inhibition of key proteins, we find that human cells unable to initiate DNA replication prematurely enter mitosis. Preventing DNA replication licensing and/or firing causes prompt activation of CDK1 and PLK1 in S phase. In the presence of DNA replication, inhibition of CHK1 and p38 leads to premature activation of mitotic kinases, which induces severe replication stress. Our results demonstrate that, rather than merely a cell cycle output, DNA replication is an integral signaling component that restricts activation of mitotic kinases. DNA replication thus functions as a brake that determines cell cycle duration.

Indexed as

MitosisS PhaseCDC2 Protein KinaseCell Cycle ProteinsCell Line, TumorCheckpoint Kinase 1Enzyme ActivationHumansp38 Mitogen-Activated Protein KinasesPolo-Like Kinase 1Protein Serine-Threonine KinasesProto-Oncogene ProteinsCDC2 Protein KinaseCDK1 protein, humanCell Cycle ProteinsCheckpoint Kinase 1CHEK1 protein, humanp38 Mitogen-Activated Protein KinasesPolo-Like Kinase 1Protein Serine-Threonine KinasesProto-Oncogene ProteinsCDK1cell cycleDNA replicationG2 phasemitosisPLK1replication checkpointS phase

Identifiers

PMID30008317
PMCPMC6039720
OpenAlexW2810264792

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.