Evidence map›Paper›PMID 40940326›Full record

ArticleNature communications2025

Temporal control of human DNA replication licensing by CDK4/6-RB signalling and chemical genetics.

Anastasia Sosenko Piscitello, Ann-Sofie Nilsson, Michael Hawgood, Abid H Sayyid, Vasilis S Dionellis, Giovanni Giglio, Bruno Urién, Pratikiran Bajgain, Sotirios G Ntallis, Jiri Bartek and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

12 authors.

Anastasia Sosenko Piscitello *Department of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland.
Ann-Sofie Nilsson *Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden.
Michael Hawgood *Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-3886-7534
Abid H SayyidDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden.ORCID http://orcid.org/0009-0001-7956-8947
Vasilis S DionellisDepartment of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland.
Giovanni GiglioDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden.ORCID http://orcid.org/0009-0009-0349-3756
Bruno UriénDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden.ORCID http://orcid.org/0009-0006-8205-6578
Pratikiran BajgainDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden.ORCID http://orcid.org/0009-0003-0686-3253
Sotirios G NtallisDepartment of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland.ORCID http://orcid.org/0000-0002-6093-8979
Jiri BartekDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden. jb@cancer.dk.ORCID http://orcid.org/0000-0003-2013-7525
Thanos D HalazonetisDepartment of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland. thanos.halazonetis@unige.ch.ORCID http://orcid.org/0000-0001-8384-5030
Bennie LemmensDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden. bennie.lemmens@ki.se.ORCID http://orcid.org/0000-0001-8051-1676

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cyclin-dependent kinases (CDKs) coordinate DNA replication and cell division, and play key roles in tissue homeostasis, genome stability and cancer development. The first step in replication is origin licensing, when minichromosome maintenance (MCM) helicases are loaded onto DNA by CDC6, CDT1 and the origin recognition complex (ORC). In yeast, origin licensing starts when CDK activity plummets in G1 phase, reinforcing the view that CDKs inhibit licensing. Here we show that, in human cells, CDK4/6 activity promotes origin licensing. By combining rapid protein degradation and time-resolved EdU-sequencing, we find that CDK4/6 activity acts epistatically to CDC6 and CDT1 in G1 phase and counteracts RB pocket proteins to promote origin licensing. Therapeutic CDK4/6 inhibitors block MCM and ORC6 loading, which we exploit to trigger mitosis with unreplicated DNA in p53-deficient cells. The CDK4/6-RB axis thus links replication licensing to proliferation, which has implications for human cell fate control and cancer therapy design.

Indexed as

Cyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6DNA ReplicationRetinoblastoma ProteinCell Cycle ProteinsG1 PhaseHumansMinichromosome Maintenance ProteinsMitosisNuclear ProteinsOrigin Recognition ComplexSignal TransductionCDC6 protein, humanCDK4 protein, humanCDK6 protein, humanCDT1 protein, humanCell Cycle ProteinsCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Minichromosome Maintenance ProteinsNuclear ProteinsOrigin Recognition ComplexRetinoblastoma Protein

Identifiers

PMID40940326
PMCPMC12432183

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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.