Evidence map›Paper›PMID 39360631›Full record

ArticleNucleic acids research2024

Altered dNTP pools accelerate tumor formation in mice.

Phong Tran, Pradeep Mishra, Leonard G Williams, Roman Moskalenko, Sushma Sharma, Anna Karin Nilsson, Danielle L Watt, Pernilla Andersson, Anders Bergh, Zachary F Pursell and 1 more

Abstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. RRM2B deficiency causes dATP and dGTP depletion through enhanced degradation and slower synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. 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

11 authors.

Phong TranDepartment of Medical Biochemistry and Biophysics, Umeå University, Linnaeus väg 6, Umeå, SE 90736, Sweden.
Pradeep MishraDepartment of Medical Biochemistry and Biophysics, Umeå University, Linnaeus väg 6, Umeå, SE 90736, Sweden.
Leonard G WilliamsDepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112, USA.
Roman MoskalenkoDepartment of Pathology, Sumy State University, Kharkivska st. 116, Sumy 40007, Ukraine.
Sushma SharmaDepartment of Medical Biochemistry and Biophysics, Umeå University, Linnaeus väg 6, Umeå, SE 90736, Sweden.
Anna Karin NilssonDepartment of Medical Biochemistry and Biophysics, Umeå University, Linnaeus väg 6, Umeå, SE 90736, Sweden.
Danielle L WattDepartment of Medical Biochemistry and Biophysics, Umeå University, Linnaeus väg 6, Umeå, SE 90736, Sweden.
Pernilla AnderssonPathology Unit, Department of Medical Biosciences, Umeå University, Daniel Naezéns väg 6M, Umeå, SE 90737, Sweden.
Anders BerghPathology Unit, Department of Medical Biosciences, Umeå University, Daniel Naezéns väg 6M, Umeå, SE 90737, Sweden.
Zachary F PursellDepartment of Biochemistry and Molecular Biology, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112, USA.ORCID 0000-0001-5871-7192
Andrei ChabesDepartment of Medical Biochemistry and Biophysics, Umeå University, Linnaeus väg 6, Umeå, SE 90736, Sweden.ORCID 0000-0003-1708-8259

Funding

Investigation of human DNA polymerase epsilon variantsR01ES028271 · NIEHS · TULANE UNIVERSITY OF LOUISIANA · PI Zachary F Pursell · 2017 to 2026
$3.6M
Foundation for the National Institutes of Health R01ES028271NIEHS NIH HHS R01 ES028271Swedish Cancer Society 22 2377 PjSwedish Research Council 2022-00675_VRTulane University
6 · The paper itself

Abstract

Alterations in deoxyribonucleoside triphosphate (dNTP) pools have been linked to increased mutation rates and genome instability in unicellular organisms and cell cultures. However, the role of dNTP pool changes in tumor development in mammals remains unclear. In this study, we present a mouse model with a point mutation at the allosteric specificity site of ribonucleotide reductase, RRM1-Y285A. This mutation reduced ribonucleotide reductase activity, impairing the synthesis of deoxyadenosine triphosphate (dATP) and deoxyguanosine triphosphate (dGTP). Heterozygous Rrm1+/Y285A mice exhibited distinct alterations in dNTP pools across various organs, shorter lifespans and earlier tumor onset compared with wild-type controls. Mutational spectrum analysis of tumors revealed two distinct signatures, one resembling a signature extracted from a human cancer harboring a mutation of the same amino acid residue in ribonucleotide reductase, RRM1Y285C. Our findings suggest that mutations in enzymes involved in dNTP metabolism can serve as drivers of cancer development.

Indexed as

Ribonucleoside Diphosphate ReductaseAnimalsDeoxyadenine NucleotidesDeoxyguanine NucleotidesDeoxyribonucleotidesFemaleHumansMiceMice, Inbred C57BLNeoplasmsPoint Mutation2'-deoxyadenosine triphosphateDeoxyadenine NucleotidesDeoxyguanine Nucleotidesdeoxyguanosine triphosphateDeoxyribonucleotidesRibonucleoside Diphosphate Reductase

Identifiers

PMID39360631
PMCPMC11551754

What OpenQuestion holds

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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.