Evidence map›Paper›PMID 40207632›Full record

ArticleNucleic acids research2025

The PIN1-p38-CtIP signalling axis protects stalled replication forks from deleterious degradation.

Francesca Vivalda, Marco Gatti, Letizia Manfredi, Hülya Dogan, Antonio Porro, Giulio Collotta, Ilaria Ceppi, Christine von Aesch, Vanessa van Ackeren, Sebastian Wild and 9 more

Abstract read
PubMed Full text at PMC Publisher
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 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. 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

19 authors.

Francesca VivaldaInstitute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
Marco GattiInstitute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
Letizia ManfrediInstitute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
Hülya DoganInstitute of Animal Pathology and Bern Center for Precision Medicine, University of Bern, 3001 Bern, Switzerland.
Antonio PorroInstitute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
Giulio CollottaInstitute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
Ilaria CeppiInstitute for Research in Biomedicine, Università della Svizzera italiana, 6500 Bellinzona, Switzerland.
Christine von AeschInstitute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
Vanessa van AckerenInstitute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
Sebastian WildInstitute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.
Martin StegerNEOsphere Biotechnologies, 82152 Martinsried, Germany.
Begoña CanovasInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.
Monica Cubillos-RojasInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.
Antoni RieraInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.
Petr CejkaInstitute for Research in Biomedicine, Università della Svizzera italiana, 6500 Bellinzona, Switzerland.ORCID 0000-0002-9087-032X
Angel R NebredaInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.
Diego DibitettoInstitute of Animal Pathology and Bern Center for Precision Medicine, University of Bern, 3001 Bern, Switzerland.
Sven RottenbergInstitute of Animal Pathology and Bern Center for Precision Medicine, University of Bern, 3001 Bern, Switzerland.
Alessandro A SartoriInstitute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland.ORCID 0000-0003-2770-0333

Funding

AIRCEuropean Union ERC-2019-AdG-883877Swiss National Science Foundation 31003A_176161UZH Candoc FK-23-050
6 · The paper itself

Abstract

Human CtIP plays a critical role in homologous recombination (HR) by promoting the resection of DNA double-strand breaks. Moreover, CtIP maintains genome stability through protecting stalled replication forks from nucleolytic degradation. However, the upstream signalling mechanisms governing the molecular switch between these two CtIP-dependent processes remain largely elusive. Here, we show that phosphorylation of CtIP by the p38α stress kinase and subsequent PIN1-mediated CtIP cis-to-trans isomerization is required for fork stabilization but dispensable for HR. We found that stalled forks are degraded in cells expressing non-phosphorylatable CtIP or lacking PIN1-p38α activity, while expression of a CtIP trans-locked mutant overcomes the requirement for PIN1-p38α in fork protection. We further reveal that Brca1-deficient mammary tumour cells that have acquired PARP inhibitor (PARPi) resistance regain chemosensitivity after PIN1 or p38α inhibition. Collectively, our findings identify the PIN1-p38-CtIP signalling pathway as a critical regulator of replication fork integrity.

Indexed as

Carrier ProteinsDNA ReplicationMitogen-Activated Protein Kinase 14NIMA-Interacting Peptidylprolyl IsomeraseNuclear Proteinsp38 Mitogen-Activated Protein KinasesBRCA1 ProteinCell Line, TumorDNA Breaks, Double-StrandedEndodeoxyribonucleasesHumansPhosphorylationPoly(ADP-ribose) Polymerase InhibitorsSignal TransductionBRCA1 ProteinCarrier ProteinsEndodeoxyribonucleasesMitogen-Activated Protein Kinase 14NIMA-Interacting Peptidylprolyl IsomeraseNuclear Proteinsp38 Mitogen-Activated Protein KinasesPIN1 protein, humanPoly(ADP-ribose) Polymerase InhibitorsRBBP8 protein, human

Identifiers

PMID40207632
PMCPMC11983131

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LicenceCC BY-NC
Read underepoch 390

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.