Evidence map›Paper›PMID 40323014›Full record

ArticleNucleic acids research2025

Human DNA replication initiation sites are specified epigenetically by oxidation of 5-methyl-deoxycytidine.

Torsten Krude, Jiaming Bi, Rachel Doran, Rebecca A Jones, James C Smith

Abstract read
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

5 authors.

Torsten KrudeDepartment of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.ORCID 0000-0002-1842-1933
Jiaming BiDepartment of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
Rachel DoranDepartment of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
Rebecca A JonesDevelopmental Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
James C SmithDevelopmental Biology Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.

Funding

Cancer Research UK CC1064Cancer Research UK FC001157Francis Crick InstituteSir Isaac Newton Trust in Cambridge 18.07ii(c)UK Medical Research Council CC1064University of CambridgeWellcome Trust CC1064Wellcome Trust FC001157Wellcome Trust Equipment WT079204
6 · The paper itself

Abstract

DNA replication initiates at tens of thousands of sites on the human genome during each S phase. However, no consensus DNA sequence has been found that specifies the locations of these replication origins. Here, we investigate modifications of human genomic DNA by density equilibrium centrifugation and DNA sequencing. We identified short discrete sites with increased density during quiescence and G1 phase that overlap with DNA replication origins before their activation in S phase. The increased density is due to the oxidation of 5-methyl-deoxycytidines by ten-eleven-translocation DNA dioxygenase (TET) enzymes at GC-rich domains. Reversible inhibition of de novo methylation and of subsequent oxidation of deoxycytidines results in a reversible inhibition of DNA replication and of cell proliferation. Our findings suggest a mechanism for the epigenetic specification and semiconservative inheritance of DNA replication origin sites in human cells that also provides a stable integral DNA replication licence to support once-per-cell cycle control of origin activation.

Indexed as

DeoxycytidineDNA ReplicationEpigenesis, GeneticReplication OriginDNADNA MethylationHumansOxidation-Reduction5-methyldeoxycytidineDeoxycytidineDNA

Identifiers

PMID40323014
PMCPMC12051107

What OpenQuestion holds

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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.