Evidence map›Paper›PMID 38175749›Full record

ArticleCell reports2024

TREX2 deficiency suppresses spontaneous and genotoxin-associated mutagenesis.

Teresa Marple, Mi Young Son, Xiaodong Cheng, Jun Ho Ko, Patrick Sung, Paul Hasty

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.6field-weighted citation impact, top 36% of its field
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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. 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

6 authors at 2 institutions in 1 country.

Teresa MarpleDepartment of Molecular Medicine and Institute of Biotechnology, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
Mi Young SonDepartment of Molecular Medicine and Institute of Biotechnology, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Department of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
Xiaodong ChengDepartment of Molecular Medicine and Institute of Biotechnology, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
Jun Ho KoDepartment of Molecular Medicine and Institute of Biotechnology, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
Patrick SungDepartment of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, TX 78229, USA; The Mays Cancer Center, University of Texas Health San Antonio MD Anderson Cancer Center, San Antonio, TX 78229, USA; Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
Paul HastyDepartment of Molecular Medicine and Institute of Biotechnology, University of Texas Health San Antonio, San Antonio, TX 78229, USA; The Mays Cancer Center, University of Texas Health San Antonio MD Anderson Cancer Center, San Antonio, TX 78229, USA; Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, TX 78229, USA. Electronic address: hastyhsc@gmail.com.
The University of Texas Health Science Center at San Antonio · USThe University of Texas MD Anderson Cancer Center · US

Funding

THE IMPACT OF CELLULAR DEFENSE ON THE ROLE OF Ku80 IN GENOME MAINTENANCE AND LONGP01AG017242 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI VIJG, JAN · 1999 to 2023
$46.1M
Mechanisms of DNA Homology-directed Genome Repair and Tumor SuppressionR35CA241801 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI SUNG, PATRICK · 2019 to 2025
$6.0M
How does TREX2 maintain and alter chromosomes?R01CA188032 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI HASTY, EDWARD PAUL, MONTAGNA, CRISTINA · 2014 to 2018
$1.8M
Study DNA repair in preventing MDS and AML after radiation and benzene exposureR01ES022054 · NIEHS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI HASTY, EDWARD PAUL · 2012 to 2016
$1.7M
NCI NIH HHS R01 CA188032NCI NIH HHS R35 CA241801NIA NIH HHS P01 AG017242NIEHS NIH HHS R01 ES022054
6 · The paper itself

Abstract

TREX2, a 3'-5' exonuclease, is a part of the DNA damage tolerance (DDT) pathway that stabilizes replication forks (RFs) by ubiquitinating PCNA along with the ubiquitin E3 ligase RAD18 and other DDT factors. Mismatch repair (MMR) corrects DNA polymerase errors, including base mismatches and slippage. Here we demonstrate that TREX2 deletion reduces mutations in cells upon exposure to genotoxins, including those that cause base lesions and DNA polymerase slippage. Importantly, we show that TREX2 generates most of the spontaneous mutations in MMR-mutant cells derived from mice and people. TREX2-induced mutagenesis is dependent on the nuclease and DNA-binding attributes of TREX2. RAD18 deletion also reduces spontaneous mutations in MMR-mutant cells, albeit to a lesser degree. Inactivation of both MMR and TREX2 additively increases RF stalls, while it decreases DNA breaks, consistent with a synthetic phenotype.

Indexed as

DNA-Directed DNA PolymeraseMutagensAnimalsDNA-Binding ProteinsDNA ReplicationExodeoxyribonucleasesHumansMiceMutagenesisMutationPhosphoproteinsUbiquitinUbiquitin-Protein LigasesDNA-Binding ProteinsDNA-Directed DNA PolymeraseExodeoxyribonucleasesMutagensPhosphoproteinsRAD18 protein, humanTREX2 protein, humanUbiquitinUbiquitin-Protein LigasesCP: Molecular biologyDNA damage tolerancemismatch repairreplication fork maintenanceTREX2

Identifiers

PMID38175749
PMCPMC10883656
OpenAlexW4390546679

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.