Evidence mapPaperPMID 41372167Full record

ArticleNature communications2025

SLFN11 counteracts the RFWD3-PRIMPOL DNA damage tolerance axis to restrain gapped DNA synthesis in response to replication stress.

Kate E Coleman, Dong-Woo Shin, Liana Goehring, Beata Szeitz, David Fenyö, Eli Rothenberg, John T Poirier, Tony T Huang

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 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. 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

8 authors.

Kate E Coleman *Department of Biochemistry & Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA.
Dong-Woo Shin *Vilcek Institute of Graduate Biomedical Sciences, NYU Grossman School of Medicine, New York, USA.ORCID http://orcid.org/0009-0003-5909-972X
Liana Goehring *Department of Biochemistry & Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA.
Beata SzeitzDepartment of Biochemistry & Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA.
David FenyöDepartment of Biochemistry & Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA.
Eli RothenbergDepartment of Biochemistry & Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-1382-1380
John T PoirierDepartment of Medicine, Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY, USA. John.Poirier@nyulangone.org.ORCID http://orcid.org/0000-0001-9795-5644
Tony T HuangDepartment of Biochemistry & Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA. Tony.huang@nyulangone.org.ORCID http://orcid.org/0000-0001-9291-5002

Funding

Tumor Immunology (TIM) Research ProgramP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 1985 to 2025
$21.1M
Project 4: Single-molecule studies defining molecular and cellular requirements for Pol θP01CA247773 · UNIV OF NORTH CAROLINA CHAPEL HILL · 2025 to 2025
$2.4M
Mechanisms of Human DNA Double-Strand Break Repair via Quantitative Single-Molecule ImagingR35GM134947 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 to 2025
$2.0M
SCLC Model Generation and Therapeutic AnalysisP01CA288368 · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2025 to 2025
$1.9M
Defining the molecular basis of oncogene-induced replication stressR01ES031658 · NIEHS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 to 2025
$1.7M
Understanding the mechanistic role of genome stability pathways in regulating cell homeostasisR35GM139610 · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2025 to 2025
$424k
NCI NIH HHS P01 CA247773NCI NIH HHS P01 CA288368NCI NIH HHS P30 CA016087NIAID NIH HHS R01 AI153040NIEHS NIH HHS R01 ES031658NIGMS NIH HHS R35 GM134947NIGMS NIH HHS R35 GM139610U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P01CA288368U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS) ES031658U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) GM139610
6 · The paper itself

Abstract

Schlafen family member 11 (SLFN11) expression sensitizes cells to a spectrum of DNA-damaging chemotherapies. Previous studies have shown that SLFN11 is recruited to stalled replication forks in response to replication stress; however, the role of SLFN11 at stressed replication forks remains unclear. Using single-molecule DNA fiber analysis and super-resolution microscopy to interrogate the dynamics of individual replication forks, we show that SLFN11 acts upon stalled replication forks to suppress efficient fork restart. In the absence of SLFN11 expression, fork restart proceeds through a pathway involving the ubiquitin ligase RFWD3 and the DNA primase-polymerase PRIMPOL to facilitate gapped DNA synthesis, thereby ensuring that cells do not accumulate replication-associated DNA damage. SLFN11 antagonizes this pathway by disrupting recruitment of RFWD3 and PRIMPOL to stalled forks in a manner dependent on a functional ATPase domain and persistent fork localization, but not on tRNA hydrolysis or ssDNA binding. Collectively, our results provide a mechanistic basis for how SLFN11 can counteract DNA damage tolerance by suppressing the RFWD3-PRIMPOL fork restart pathway.

Indexed as

DNA DamageDNA-Directed DNA PolymeraseDNA PrimaseDNA ReplicationMultifunctional EnzymesNuclear ProteinsUbiquitin-Protein LigasesDNADNA Damage ToleranceHumansDNADNA-Directed DNA PolymeraseDNA PrimaseMultifunctional EnzymesNuclear ProteinsPrimPol protein, humanSLFN11 protein, humanUbiquitin-Protein Ligases

Identifiers

PMID41372167
PMCPMC12696100

What Socratic holds

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LicenceCC BY
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 Socratic graph.