Evidence map›Paper›PMID 39920158›Full record

ArticleNature communications2025

D-2-hydroxyglutarate impairs DNA repair through epigenetic reprogramming.

Fengchao Lang, Karambir Kaur, Haiqing Fu, Javeria Zaheer, Diego Luis Ribeiro, Mirit I Aladjem, Chunzhang Yang

Abstract read
PubMed Full text at PMC Publisher
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 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Article
  2. Review
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  5. Article
  6. Review
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  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Epigenetic alterations in Myeloid Malignancies.Advances in experimental medicine and biology · 2026
    Review
  15. Article
  16. Article
  17. Article
  18. 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

7 authors.

Fengchao Lang *Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Karambir Kaur *Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Haiqing FuDevelopmental Therapeutic Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-4764-1422
Javeria ZaheerNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Diego Luis RibeiroNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-1715-966X
Mirit I AladjemDevelopmental Therapeutic Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-1875-3110
Chunzhang YangNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. yangc2@nih.gov.ORCID http://orcid.org/0000-0001-6433-0867

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer-associated mutations in IDH are associated with multiple types of human malignancies, which exhibit distinctive metabolic reprogramming, production of oncometabolite D-2-HG, and shifted epigenetic landscape. IDH mutated malignancies are signatured with "BRCAness", highlighted with the sensitivity to DNA repair inhibitors and genotoxic agents, although the underlying molecular mechanism remains elusive. In the present study, we demonstrate that D-2-HG impacts the chromatin conformation adjustments, which are associated with DNA repair process. Mechanistically, D-2-HG diminishes the chromatin interactions in the DNA damage regions via revoking CTCF binding. The hypermethylation of cytosine, resulting from the suppression of TET1 and TET2 activities by D-2-HG, contributes to the dissociation of CTCF from DNA damage regions. CTCF depletion leads to the disruption of chromatin organization around the DNA damage sites, which abolishes the recruitment of essential DNA damage repair proteins BRCA2 and RAD51, as well as impairs homologous repair in the IDH mutant cancer cells. These findings provide evidence that CTCF-mediated chromatin interactions play a key role in DNA damage repair proceedings. Oncometabolites jeopardize genome stability and DNA repair by affecting high-order chromatin structure.

Indexed as

DNA RepairEpigenesis, GeneticGlutaratesBRCA2 ProteinCCCTC-Binding FactorCell Line, TumorChromatinDioxygenasesDNA-Binding ProteinsDNA DamageDNA MethylationGenomic InstabilityHumansIsocitrate DehydrogenaseMixed Function OxygenasesMutationalpha-hydroxyglutarateBRCA2 ProteinBRCA2 protein, humanCCCTC-Binding FactorChromatinCTCF protein, humanDioxygenasesDNA-Binding ProteinsGlutaratesIsocitrate DehydrogenaseMixed Function OxygenasesProto-Oncogene ProteinsRAD51 protein, humanRad51 RecombinaseTET1 protein, humanTET2 protein, human

Identifiers

PMID39920158
PMCPMC11806014

What OpenQuestion holds

Textmetadata
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.