Evidence map›Paper›PMID 41812883›Full record

ArticleThe Journal of biological chemistry2026

ISGylation of γH2AX retains MDC1 and facilitates homologous recombination repair causing radioresistance in esophageal adenocarcinoma.

Archismaan Ghosh, Paramita Ray, Dafydd Thomas, Vinay Jeeyar, Shreya Pillai, Venkatesha Basrur, Irina V Bondarenko, Emily Bellile, David H Wang, Meredith A Morgan and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Archismaan GhoshDepartment of Radiation Oncology, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
Paramita RayDepartment of Radiation Oncology, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
Dafydd ThomasDepartment of Pathology, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
Vinay JeeyarDepartment of Radiation Oncology, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
Shreya PillaiDepartment of Radiation Oncology, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
Venkatesha BasrurDepartment of Pathology, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
Irina V BondarenkoDepartment of Biostatistics, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
Emily BellileDepartment of Biostatistics, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
David H WangVA Medical Center, Ann Arbor, Michigan, USA.
Meredith A MorganDepartment of Radiation Oncology, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
Qiang ZhangDepartment of Radiation Oncology, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
David G BeerDepartment of Surgery, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
Kiran H LagisettyDepartment of Surgery, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
Theodore S LawrenceDepartment of Radiation Oncology, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
Dipankar RayDepartment of Radiation Oncology, The University of Michigan Medical School, Ann Arbor, Michigan, USA. Electronic address: dipray@umich.edu.

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Eric R. Fearon · 1988 to 2026
$178.2M
Translational Pathology CoreP50CA269022 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE, Meredith A Morgan · 2023 to 2026
$10.0M
Targeting the DNA damage response in combination with radiation to induce innate immunity and improve immunotherapy efficacy in pancreatic cancerR01CA240515 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORGAN, MEREDITH A · 2020 to 2024
$2.2M
NCI NIH HHS P30 CA046592NCI NIH HHS P50 CA269022NCI NIH HHS R01 CA240515
6 · The paper itself

Abstract

High expression of interferon-stimulated gene 15 (ISG15) has been associated with poor survival in patients with esophageal adenocarcinoma (EAC). Like ubiquitin, ISG15 utilizes its C-terminal LRGG motif to post-translationally modify target proteins through a process called ISGylation, thereby influencing their stability, function, and interaction networks. Given ISG15's role in the replication stress response, we hypothesized that it may also contribute to DNA repair mechanisms. We found that ISG15 is upregulated following ionizing radiation (IR), and its knockdown disrupts the IR-induced G2/M checkpoint, leading to increased radiosensitivity in EAC cells. In synchronized cells, ISG15 expression peaks during the S/G2 phases. Knockdown of ISG15 impairs homologous recombination repair (HRR) with compensatory upregulation of non-homologous end joining (NHEJ). Similarly, cells expressing an ISGylation-defective ISG15

Indexed as

Adaptor Proteins, Signal TransducingAdenocarcinomaCell Cycle ProteinsCytokinesEsophageal NeoplasmsHistonesRadiation ToleranceRecombinational DNA RepairTrans-ActivatorsUbiquitinsCell Line, TumorHumansAdaptor Proteins, Signal TransducingCell Cycle ProteinsCytokinesH2AX protein, humanHistonesISG15 protein, humanMDC1 protein, humanTrans-ActivatorsUbiquitinsesophageal adenocarcinomaH2AXhomologous recombination repair (HRR)ISGylationradioresistance

Identifiers

PMID41812883
PMCPMC13084363

What OpenQuestion holds

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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.