Evidence map›Paper›PMID 39607700›Full record

ArticleNucleic acids research2024

DNA sequence and lesion-dependent mitochondrial transcription factor A (TFAM)-DNA-binding modulates DNA repair activities and products.

Kathleen Urrutia, Yu Hsuan Chen, Jin Tang, Ta I Hung, Guodong Zhang, Wenyan Xu, Wenxin Zhao, Dylan Tonthat, Chia-En A Chang, Linlin Zhao

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
  2. hexABC seeking the physical code of DNA.Nature communications · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025
    Review
  7. Mitochondria-Nuclear Crosstalk: Orchestrating mtDNA Maintenance.Environmental and molecular mutagenesis · 2025
    Review
  8. Article
  9. 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

10 authors.

Kathleen UrrutiaDepartment of Chemistry, University of California, Riverside, CA 92521, USA.
Yu Hsuan ChenDepartment of Chemistry, University of California, Riverside, CA 92521, USA.
Jin TangDepartment of Chemistry, University of California, Riverside, CA 92521, USA.
Ta I HungDepartment of Chemistry, University of California, Riverside, CA 92521, USA.
Guodong ZhangDepartment of Chemistry, University of California, Riverside, CA 92521, USA.
Wenyan XuDepartment of Chemistry, University of California, Riverside, CA 92521, USA.ORCID 0000-0003-2034-2828
Wenxin ZhaoDepartment of Chemistry, University of California, Riverside, CA 92521, USA.
Dylan TonthatDepartment of Chemistry, University of California, Riverside, CA 92521, USA.
Chia-En A ChangDepartment of Chemistry, University of California, Riverside, CA 92521, USA.
Linlin ZhaoDepartment of Chemistry, University of California, Riverside, CA 92521, USA.ORCID 0000-0002-8821-4198

Funding

Chemical and Molecular Mechanisms of Mitochondrial DNA DegradationR35GM128854 · NIGMS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Linlin Zhao · 2018 to 2026
$3.1M
Next-Generation GPU Computing Resource for Simulating Ligand-Protein Binding Kinetics/MechanismR01GM109045 · NIGMS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI CHANG, CHIA-EN · 2014 to 2023
$2.8M
National Science Foundation CHE130009NIGMS NIH HHS R01 GM109045NIGMS NIH HHS R35 GM128854University of California
6 · The paper itself

Abstract

Mitochondrial DNA (mtDNA) is indispensable for mitochondrial function and is maintained by DNA repair, turnover, mitochondrial dynamics and mitophagy, along with the inherent redundancy of mtDNA. Base excision repair (BER) is a major DNA repair mechanism in mammalian mitochondria. Mitochondrial BER enzymes are implicated in mtDNA-mediated immune response and inflammation. mtDNA is organized into mitochondrial nucleoids by mitochondrial transcription factor A (TFAM). The regulation of DNA repair activities by TFAM-DNA interactions remains understudied. Here, we demonstrate the modulation of DNA repair enzymes by TFAM concentrations, DNA sequences and DNA modifications. Unlike previously reported inhibitory effects, we observed that human uracil-DNA glycosylase 1 (UNG1) and AP endonuclease I (APE1) have optimal activities at specific TFAM/DNA molar ratios. High TFAM/DNA ratios inhibited other enzymes, OGG1 and AAG. In addition, TFAM reduces the accumulation of certain repair intermediates. Molecular dynamics simulations and DNA-binding experiments demonstrate that the presence of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in certain sequence motifs enhances TFAM-DNA binding, partially explaining the inhibition of OGG1 activity. Bioinformatic analysis of published 8-oxodG, dU, and TFAM-footprint maps reveals a correlation between 8-oxodG and TFAM locations in mtDNA. Collectively, these results highlight the complex regulation of mtDNA repair by DNA sequence, TFAM concentrations, lesions and repair enzymes.

Indexed as

DNA-Binding ProteinsDNA GlycosylasesDNA, MitochondrialDNA RepairMitochondrial ProteinsTranscription FactorsUracil-DNA GlycosidaseBase SequenceDNADNA-(Apurinic or Apyrimidinic Site) LyaseDNA DamageHumansMolecular Dynamics SimulationProtein BindingDNADNA-(Apurinic or Apyrimidinic Site) LyaseDNA-Binding ProteinsDNA GlycosylasesDNA, MitochondrialMitochondrial Proteinsmitochondrial transcription factor Aoxoguanine glycosylase 1, humanTFAM protein, humanTranscription FactorsUracil-DNA Glycosidase

Identifiers

PMID39607700
PMCPMC11662936

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.