Evidence map›Paper›PMID 38897003›Full record

ArticleDNA repair2024

Oncometabolite 2-hydroxyglutarate suppresses basal protein levels of DNA polymerase beta that enhances alkylating agent and PARG inhibition induced cytotoxicity.

Kate M Saville, Rasha Q Al-Rahahleh, Aisha H Siddiqui, Morgan E Andrews, Wynand P Roos, Christopher A Koczor, Joel F Andrews, Faisal Hayat, Marie E Migaud, Robert W Sobol

Abstract read
In one paragraph

Article in DNA repair, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
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  4. Review
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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

10 authors.

Kate M SavilleDepartment of Pharmacology & Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, United States.
Rasha Q Al-RahahlehDepartment of Pharmacology & Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, United States; Department of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI 02912, United States.
Aisha H SiddiquiDepartment of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI 02912, United States.
Morgan E AndrewsDepartment of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI 02912, United States.
Wynand P RoosDepartment of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI 02912, United States.
Christopher A KoczorDepartment of Pharmacology & Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, United States.
Joel F AndrewsDepartment Biochemistry and Molecular Biology & Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, United States.
Faisal HayatDepartment of Pharmacology & Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, United States.
Marie E MigaudDepartment of Pharmacology & Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, United States.
Robert W SobolDepartment of Pharmacology & Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, United States; Department of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI 02912, United States. Electronic address: rwsobol@brown.edu.

Funding

TR&D 3 - Network Guided Machine LearningP41GM103504 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2012 to 2024
$17.3M
A Systems Approach to Mapping the DNA Damage ResponseR01ES014811 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2005 to 2021
$8.6M
Research Project 3P01ES028949 · NIEHS · FLORIDA GULF COAST UNIVERSITY · PI PARSONS, MICHAEL · 2018 to 2024
$3.8M
Novel approaches to enhance tumor cell cytotoxicity of alkylating agentsR01CA148629 · NCI · UNIVERSITY OF SOUTH ALABAMA · PI SOBOL, ROBERT W · 2010 to 2021
$3.4M
Investigating genetic ancestry influences on oral cavity and laryngeal cancer survival disparitiesR01CA238061 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI RAGIN, CAMILLE C., SOBOL, ROBERT W · 2019 to 2023
$3.4M
Measuring genomic DNA damage and DNA repair capacity in longitudinal population samples - a step towards precision preventionU01ES029518 · NIEHS · UNIVERSITY OF SOUTH ALABAMA · PI SOBOL, ROBERT W · 2018 to 2022
$2.7M
Barcoded human cells engineered with heterozygous genetic diversity to uncover toxicodynamic variabilityR44ES032522 · NIEHS · AMELIA TECHNOLOGIES, LLC · PI GEORGE, JAY, SOBOL, ROBERT W · 2021 to 2023
$1.9M
The Paternal Age Effect - Enhanced Germ Cell Mutagenesis Modulated by the TRP53/APE1/MDM2 Tumor Suppressor AxisR01AG069740 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI KRAIG, ELLEN · 2020 to 2024
$1.8M
SON-mediated RNA splicing in glioblastomaR01CA236911 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI AHN, ERIN EUN-YOUNG · 2020 to 2024
$1.8M
B-vitamins and NAD mechanism, or when vitamin B3's bioavailability is not enough.R21AT009908 · NCCIH · UNIVERSITY OF SOUTH ALABAMA · PI MIGAUD, MARIE EUGENIE · 2018 to 2019
$423k
NCCIH NIH HHS R21 AT009908NCI NIH HHS R01 CA148629NCI NIH HHS R01 CA236911NCI NIH HHS R01 CA238061NIA NIH HHS R01 AG069740NIEHS NIH HHS P01 ES028949NIEHS NIH HHS R01 ES014811NIEHS NIH HHS R44 ES032522NIEHS NIH HHS U01 ES029518NIGMS NIH HHS P41 GM103504
6 · The paper itself

Abstract

Mutations in isocitrate dehydrogenase isoform 1 (IDH1) are primarily found in secondary glioblastoma (GBM) and low-grade glioma but are rare in primary GBM. The standard treatment for GBM includes radiation combined with temozolomide, an alkylating agent. Fortunately, IDH1 mutant gliomas are sensitive to this treatment, resulting in a more favorable prognosis. However, it's estimated that up to 75 % of IDH1 mutant gliomas will progress to WHO grade IV over time and develop resistance to alkylating agents. Therefore, understanding the mechanism(s) by which IDH1 mutant gliomas confer sensitivity to alkylating agents is crucial for developing targeted chemotherapeutic approaches. The base excision repair (BER) pathway is responsible for repairing most base damage induced by alkylating agents. Defects in this pathway can lead to hypersensitivity to these agents due to unresolved DNA damage. The coordinated assembly and disassembly of BER protein complexes are essential for cell survival and for maintaining genomic integrity following alkylating agent exposure. These complexes rely on poly-ADP-ribose formation, an NAD

Indexed as

DNA Polymerase betaGlutaratesIsocitrate DehydrogenaseAlkylating AgentsAntineoplastic Agents, AlkylatingCell Line, TumorDNA DamageDNA RepairGliomaHumansMutationPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesTemozolomideAlkylating Agentsalpha-hydroxyglutarateAntineoplastic Agents, AlkylatingDNA Polymerase betaGlutaratesIDH1 protein, humanIsocitrate DehydrogenasePARP1 protein, humanPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesTemozolomide2-hydroxyglutarateBase excision repairDNA polymerase betaIDH1NAD(+) metabolismPARP1

Identifiers

PMID38897003
PMCPMC11239280

What Socratic 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 Socratic graph.