Evidence map›Paper›PMID 37590370›Full record

ArticleScience (New York, N.Y.)2023

In silico protein interaction screening uncovers DONSON's role in replication initiation.

Yang Lim, Lukas Tamayo-Orrego, Ernst Schmid, Zygimante Tarnauskaite, Olga V Kochenova, Rhian Gruar, Sachiko Muramatsu, Luke Lynch, Aitana Verdu Schlie, Paula L Carroll and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 1 pooled it
16.2field-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

74 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. DONSON links tumor-cell survival to MIF-associated macrophage remodeling in small cell lung cancer.Apoptosis : an international journal on programmed cell death · 2026
    Article
  5. Article
  6. Article
  7. A broadly conserved gram-positive lipoprotein regulates cell elongation.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  8. A Chromatin Biology Assessment of AlphaFold3.bioRxiv : the preprint server for biology · 2026
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. The transformative power of structural predictions with AI in plant science.The Plant journal : for cell and molecular biology · 2026
    Review
  19. Review
  20. Article

14 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

15 authors at 5 institutions in 3 countries.

Yang Lim *Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Blavatnik Institute, Boston, MA 02115, USA.ORCID 0000-0001-6880-8418
Lukas Tamayo-Orrego *MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.ORCID 0000-0001-7041-4848
Ernst SchmidDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Blavatnik Institute, Boston, MA 02115, USA.ORCID 0000-0002-4662-5298
Zygimante TarnauskaiteMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.ORCID 0000-0003-1815-1651
Olga V KochenovaDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Blavatnik Institute, Boston, MA 02115, USA.
Rhian GruarDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Blavatnik Institute, Boston, MA 02115, USA.
Sachiko MuramatsuDepartment of Chromosome Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka 411-8540, Japan.
Luke LynchBiochemistry Department, Stanford School of Medicine, Stanford, CA 94305, USA.ORCID 0000-0002-1948-2316
Aitana Verdu SchlieMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Paula L CarrollMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.ORCID 0009-0002-0339-2559
Gheorghe ChistolChemical and Systems Biology Department, Stanford School of Medicine, Stanford, CA 94305, USA.
Martin A M ReijnsMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.ORCID 0000-0002-5048-2752
Masato T KanemakiDepartment of Chromosome Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka 411-8540, Japan.ORCID 0000-0002-7657-1649
Andrew P JacksonMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.ORCID 0000-0002-8739-2646
Johannes C WalterDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Blavatnik Institute, Boston, MA 02115, USA.ORCID 0000-0002-4186-7570
Institute of Genetics and Cancer · GBHarvard University · USHoward Hughes Medical Institute · USNational Institute of Genetics · JPStanford Medicine · US

Funding

Supplement to Enhance Wellness and Resiliency in the Graduate EnvironmentT32GM007276 · NIGMS · STANFORD UNIVERSITY · PI MORRISON, ASHBY J. · 1985 to 2023
$32.9M
The Fanconi anemia pathway: role in DNA interstrand cross-link repairR01HL098316 · NHLBI · HARVARD MEDICAL SCHOOL · PI Johannes Walter · 2010 to 2026
$6.3M
Structure-Function Analysis of DNA Replication Initiation Factors Implicated in DiseaseR35GM147060 · NIGMS · STANFORD UNIVERSITY · PI Gheorghe Chistol · 2022 to 2026
$2.2M
Howard Hughes Medical InstituteMedical Research Council MC_UU_00035/10NHLBI NIH HHS R01 HL098316NIGMS NIH HHS R35 GM147060NIGMS NIH HHS T32 GM007276
6 · The paper itself

Abstract

CDC45-MCM2-7-GINS (CMG) helicase assembly is the central event in eukaryotic replication initiation. In yeast, a multi-subunit "pre-loading complex" (pre-LC) accompanies GINS to chromatin-bound MCM2-7, leading to CMG formation. Here, we report that DONSON, a metazoan protein mutated in microcephalic primordial dwarfism, is required for CMG assembly in vertebrates. Using AlphaFold to screen for protein-protein interactions followed by experimental validation, we show that DONSON scaffolds a vertebrate pre-LC containing GINS, TOPBP1, and DNA pol ε. Our evidence suggests that DONSON docks the pre-LC onto MCM2-7, delivering GINS to its binding site in CMG. A patient-derived DONSON mutation compromises CMG assembly and recapitulates microcephalic dwarfism in mice. These results unify our understanding of eukaryotic replication initiation, implicate defective CMG assembly in microcephalic dwarfism, and illustrate how in silico protein-protein interaction screening accelerates mechanistic discovery.

Indexed as

Cell Cycle ProteinsDNA-Binding ProteinsDNA ReplicationMinichromosome Maintenance ProteinsNuclear ProteinsAnimalsComputer SimulationDwarfismHumansMiceMicrocephalyProtein Interaction MappingSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsXenopus laevisCell Cycle ProteinsDNA-Binding ProteinsDONSON protein, humanMinichromosome Maintenance ProteinsNuclear ProteinsSaccharomyces cerevisiae Proteins

Identifiers

PMID37590370
PMCPMC10801813
OpenAlexW4385925982

What OpenQuestion holds

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LicenceCC BY
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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.