Evidence map›Paper›PMID 26876348›Full record

ArticleNature communications2016

A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells.

Akshay K Ahuja, Karolina Jodkowska, Federico Teloni, Anna H Bizard, Ralph Zellweger, Raquel Herrador, Sagrario Ortega, Ian D Hickson, Matthias Altmeyer, Juan Mendez and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed
13.2field-weighted citation impact, top 1% 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

126 citing papers in PubMed, 197 citations in OpenAlex.

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  19. Embryonic Stem Cell-Specific Responses to DNA Replication Stress.bioRxiv : the preprint server for biology · 2025
    Article
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66 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

11 authors at 4 institutions in 4 countries.

Akshay K AhujaInstitute of Molecular Cancer Research, University of Zurich, Zurich CH-8057, Switzerland.
Karolina JodkowskaDNA Replication Group, Molecular Oncology Programme, CNIO, Madrid E-28029, Spain.
Federico TeloniInstitute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich CH-8057, Switzerland.ORCID http://orcid.org/0000-0003-0953-8010
Anna H BizardDepartment of Cellular and Molecular Medicine, Center for Chromosome Stability and Center for Healthy Aging, University of Copenhagen, Panum Institute, Copenhagen N DK-2200, Denmark.ORCID http://orcid.org/0000-0003-1858-3999
Ralph ZellwegerInstitute of Molecular Cancer Research, University of Zurich, Zurich CH-8057, Switzerland.
Raquel HerradorInstitute of Molecular Cancer Research, University of Zurich, Zurich CH-8057, Switzerland.
Sagrario OrtegaTransgenic Mice Core Unit, Biotechnology Programme, CNIO, Madrid E-28029, Spain.
Ian D HicksonDepartment of Cellular and Molecular Medicine, Center for Chromosome Stability and Center for Healthy Aging, University of Copenhagen, Panum Institute, Copenhagen N DK-2200, Denmark.
Matthias AltmeyerInstitute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich CH-8057, Switzerland.
Juan MendezDNA Replication Group, Molecular Oncology Programme, CNIO, Madrid E-28029, Spain.
Massimo LopesInstitute of Molecular Cancer Research, University of Zurich, Zurich CH-8057, Switzerland.
University of Zurich · CHSpanish National Cancer Research Centre · ESUniversity of Copenhagen · DKCentro Nacional de Biotecnología · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Embryonic stem cells (ESCs) represent a transient biological state, where pluripotency is coupled with fast proliferation. ESCs display a constitutively active DNA damage response (DDR), but its molecular determinants have remained elusive. Here we show in cultured ESCs and mouse embryos that H2AX phosphorylation is dependent on Ataxia telangiectasia and Rad3 related (ATR) and is associated with chromatin loading of the ssDNA-binding proteins RPA and RAD51. Single-molecule analysis of replication intermediates reveals massive ssDNA gap accumulation, reduced fork speed and frequent fork reversal. All these marks of replication stress do not impair the mitotic process and are rapidly lost at differentiation onset. Delaying the G1/S transition in ESCs allows formation of 53BP1 nuclear bodies and suppresses ssDNA accumulation, fork slowing and reversal in the following S-phase. Genetic inactivation of fork slowing and reversal leads to chromosomal breakage in unperturbed ESCs. We propose that rapid cell cycle progression makes ESCs dependent on effective replication-coupled mechanisms to protect genome integrity.

Indexed as

DNA DamageDNA ReplicationG1 PhaseG1 Phase Cell Cycle CheckpointsAnimalsAtaxia Telangiectasia Mutated ProteinsBlastocystBlotting, WesternChromatinChromosomal Proteins, Non-HistoneDNA-Binding ProteinsDNA, Single-StrandedElectrophoresis, Gel, Pulsed-FieldFlow CytometryHistonesMiceAtaxia Telangiectasia Mutated ProteinsAtr protein, mouseChromatinChromosomal Proteins, Non-HistoneDNA-Binding ProteinsDNA, Single-Strandedgamma-H2AX protein, mouseHistonesPoly(ADP-ribose) PolymerasesRad51 protein, mouseRad51 RecombinaseReplication Protein ARPA32 protein, mouseTrp53bp1 protein, mouseTumor Suppressor p53-Binding Protein 1

Identifiers

PMID26876348
PMCPMC4756311
OpenAlexW2298495255

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.