Evidence map›Paper›PMID 40482467›Full record

ArticleTranslational oncology2025

POLQ mediated end-joining promotes DNA damage tolerance in neuroblastoma.

Sahiti Chukkapalli, Keyonna Williams, Biao Hu, Kimber Converso-Baran, Olivia Tussing, Patrick O'Brien, Nouri Neamati, Erika A Newman

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Beyond Short Microhomologies: Mismatch-Compatible Pol θ-Mediated DNA Damage Repair.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    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

8 authors.

Sahiti ChukkapalliDepartments of Surgery, University of Michigan, Ann Arbor, MI, USA.
Keyonna WilliamsDepartments of Surgery, University of Michigan, Ann Arbor, MI, USA.
Biao HuDepartments of Surgery, University of Michigan, Ann Arbor, MI, USA.
Kimber Converso-BaranFrankel Cardiovascular Center Physiology and Phenotyping Core, The Rogel Cancer Center, The University of Michigan, Ann Arbor, MI, USA.
Olivia TussingDepartments of Surgery, University of Michigan, Ann Arbor, MI, USA.
Patrick O'BrienBiological Chemistry, .University of Michigan, Ann Arbor, MI, USA.
Nouri NeamatiMedicinal Chemistry, University of Michigan, Ann Arbor, MI, USA.
Erika A NewmanDepartments of Surgery, University of Michigan, Ann Arbor, MI, USA. Electronic address: eanewman@med.umich.edu.

Funding

Mechanisms of Base Excision DNA RepairR35GM149546 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Patrick J O'Brien · 2023 to 2026
$1.8M
NIGMS NIH HHS R35 GM149546
6 · The paper itself

Abstract

Segmental chromosomal alterations, including 11q deletion and 17q gain, are the strongest predictors of pediatric neuroblastoma relapse. These alterations result from unbalanced translocations linked to erroneous DNA repair. Breakpoint sequence analysis suggests that these abnormalities arise through a nonhomologous end-joining mechanism, indicating a potential therapeutic opportunity. While the exact components driving this DNA end-joining process in neuroblastoma remain unknown, polymerase theta-mediated end-joining (TMEJ) has been implicated in other homologous recombination-deficient cancers. Our previous work demonstrated that high-risk neuroblastoma expresses elevated levels of TMEJ components, including DNA Ligase III and Ligase I, while downregulating classical NHEJ factors (DNA Ligase IV and Artemis). Here we show that POLQ, a critical enzyme in TMEJ, is significantly upregulated in neuroblastoma. POLQ knockout impairs proliferation, enhances sensitivity to DNA damaging agents, and reduces tumor growth in vivo. These findings suggest that POLQ facilitates DNA damage tolerance in neuroblastoma and represents a viable therapeutic target.

Indexed as

DNA repairNeuroblastomaPOLQTherapy resistance

Identifiers

PMID40482467
PMCPMC12177186

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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.