Evidence map›Paper›PMID 40748758›Full record

ArticleCell reports2025

Topoisomerase IIIα controls alternative lengthening of telomeres.

Prashant Khandagale, Yilun Sun, Daiki Taniyama, Sourav Saha, Liton Kumar Saha, Yves Pommier

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. The Roles of Topoisomerases in Transcriptional Regulation.International journal of molecular sciences · 2026
    Review
  3. Identification of aFrontiers in pharmacology · 2026
    Article
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

6 authors.

Prashant KhandagaleDevelopmental Therapeutics Branch & Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: khandagalepr@nih.gov.
Yilun SunDevelopmental Therapeutics Branch & Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Department of Pharmacology, Physiology and Drug Development, University of Maryland, School of Medicine, Baltimore, MD 21201, USA; Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA.
Daiki TaniyamaDevelopmental Therapeutics Branch & Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Sourav SahaDevelopmental Therapeutics Branch & Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Liton Kumar SahaDevelopmental Therapeutics Branch & Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Yves PommierDevelopmental Therapeutics Branch & Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: pommier@nih.gov.

Funding

PROTEIN-ASSOCIATED DNA BREAKS AS INDICATOR OF TOPOISOMERASE INHIBITIONZ01BC006150 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI POMMIER, YVES · 1996 to 2008
$1.5M
DNA TOPOISOMERASES AS TARGET OF ACTION OF ANTICANCER DRUGSZ01BC006161 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI POMMIER, YVES · 1996 to 2008
$1.5M
Investigating the role of neddylation in the repair of topoisomerase I inhibitor-induced replication damage in colorectal cancerR00CA273171 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI Yilun Sun · 2025 to 2026
$498k
Intramural NIH HHS Z01 BC006150Intramural NIH HHS Z01 BC006161NCI NIH HHS R00 CA273171
6 · The paper itself

Abstract

Alternative lengthening of telomeres (ALT) is a homologous recombination-dependent telomere elongation mechanism utilized by at least 10%-15% of all cancers. Here, we identify that the DNA topoisomerase, topoisomerase III⍺ (TOP3A), is enriched at the telomeres of ALT cells but not at the telomeres of telomerase (Tel)-positive cancer cells. We demonstrate that TOP3A stabilizes the shelterin complex in ALT cancer cell lines but not in Tel cells and that long non-coding telomeric-repeat containing RNA (TERRA) enrichment at telomeres depends on TOP3A. TOP3A also promotes the generation of single-stranded telomeric C-strand (ssTeloC) DNA, a recently discovered marker for ALT. Additionally, we find that inducing break-associated TOP3A-DNA-protein crosslinks in ALT cells suppresses TERRA enrichment and destabilizes the shelterin complex. Taken together, these observations uncover unexplored functions of TOP3A at ALT telomeres and suggest the potential of developing an ALT-specific cancer therapeutic strategy targeting TOP3A.

Indexed as

DNA Topoisomerases, Type ITelomereTelomere HomeostasisCell Line, TumorHumansShelterin ComplexTelomeraseDNA Topoisomerases, Type IShelterin ComplexTelomeraseALTAPBsBLMCP: Molecular biologyDPCshomologous recombinationssTeloCtelomereTERF2TERRATOP3A

Identifiers

PMID40748758
PMCPMC12451542

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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.