Evidence map›Paper›PMID 34826736›Full record

ArticleDNA repair2022

Mouse Embryonic Fibroblasts Isolated From Nthl1 D227Y Knockin Mice Exhibit Defective DNA Repair and Increased Genome Instability.

Carolyn G Marsden, Lipsa Das, Timothy P Nottoli, Scott D Kathe, Sylvie Doublié, Susan S Wallace, Joann B Sweasy

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in DNA repair, 2022. 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, top 89% 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

3 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Article
  3. 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

7 authors at 4 institutions in 1 country.

Carolyn G MarsdenDepartment of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, VT 05405, USA-0068.
Lipsa DasDepartment of Cellular and Molecular Medicine, University of Arizona Cancer Center, Tucson, AZ 85724-5024, USA.
Timothy P NottoliSection of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Scott D KatheDepartment of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, VT 05405, USA-0068.
Sylvie DoubliéDepartment of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, VT 05405, USA-0068.
Susan S WallaceDepartment of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, VT 05405, USA-0068.
Joann B SweasyDepartment of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, VT 05405, USA-0068; Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06510; Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, Tucson, AZ 85724-5024, USA. Electronic address: jsweasy@email.arizona.edu.
University of Vermont · USUniversity of Arizona · USUniversity of Arizona Cancer CenterYale University · US

Funding

SUBSTRATE SPECIFICITY OF THE BER OXIDATIVE DNA GLYCOSYLASESP01CA098993 · NCI · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI LEE, ANDREA J · 2004 to 2021
$25.9M
NCI NIH HHS P01 CA098993
6 · The paper itself

Abstract

Oxidative DNA damage as a result of normal cellular metabolism, inflammation, or exposure to exogenous DNA damaging agents if left unrepaired, can result in genomic instability, a precursor to cancer and other diseases. Nth-like DNA glycosylase 1 (NTHL1) is an evolutionarily conserved bifunctional DNA glycosylase that primarily removes oxidized pyrimidine lesions. NTHL1 D239Y is a germline variant identified in both heterozygous and homozygous state in the human population. Here, we have generated a knockin mouse model carrying Nthl1 D227Y (mouse homologue of D239Y) using CRISPR-cas9 genome editing technology and investigated the cellular effects of the variant in the heterozygous (Y/+) and homozygous (Y/Y) state using murine embryonic fibroblasts. We identified a significant increase in double stranded breaks, genomic instability, replication stress and impaired proliferation in both the Nthl1 D227Y heterozygous Y/+ and homozygous mutant Y/Y MEFs. Importantly, we identified that the presence of the D227Y variant interferes with repair by the WT protein, possibly by binding and shielding the lesions. The cellular phenotypes observed in D227Y mutant MEFs suggest that both the heterozygous and homozygous carriers of this NTHL1 germline mutation may be at increased risk for the development of DNA damage-associated diseases, including cancer.

Indexed as

DNA RepairGenomic InstabilityMutation, MissenseAnimalsDeoxyribonuclease (Pyrimidine Dimer)DNADNA DamageFibroblastsGene Knock-In TechniquesMiceMice, Mutant StrainsMutagensOxidative StressVitamin K 3Deoxyribonuclease (Pyrimidine Dimer)DNAMutagensNthl1 protein, mouseVitamin K 3Base excision repairGenomic instabilityNTHL1 glycosylaseOxidative DNA damage

Identifiers

PMID34826736
PMCPMC8787541
OpenAlexW3214245065

What OpenQuestion holds

Textmetadata
LicenceTDM
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.