Evidence map›Paper›PMID 28531304›Full record

ArticleNucleic acids research2017

Replication studies of carboxymethylated DNA lesions in human cells.

Jun Wu, Pengcheng Wang, Lin Li, Nicole L Williams, Debin Ji, Walter J Zahurancik, Changjun You, Jianshuang Wang, Zucai Suo, Yinsheng Wang

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

10 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Formation of Carboxymethyl-Phosphotriester Adducts in DNA.Chemical research in toxicology · 2025
    Article
  3. Metabolic Activation and DNA Interactions of CarcinogenicInternational journal of molecular sciences · 2022
    Review
  4. Review
  5. Article
  6. Article
  7. Mammalian DNA Polymerase Kappa Activity and Specificity.Molecules (Basel, Switzerland) · 2019
    Review
  8. Review
  9. DNA replication studies ofThe Journal of biological chemistry · 2019
    Article
  10. Chemical Analysis of DNA Damage.Analytical chemistry · 2018
    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 at 2 institutions in 1 country.

Jun WuDepartment of Chemistry, University of California, Riverside, CA 92521, USA.
Pengcheng WangEnvironmental Toxicology Graduate Program, University of California, Riverside, CA 92521, USA.
Lin LiDepartment of Chemistry, University of California, Riverside, CA 92521, USA.
Nicole L WilliamsEnvironmental Toxicology Graduate Program, University of California, Riverside, CA 92521, USA.
Debin JiDepartment of Chemistry, University of California, Riverside, CA 92521, USA.
Walter J ZahurancikDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
Changjun YouDepartment of Chemistry, University of California, Riverside, CA 92521, USA.
Jianshuang WangDepartment of Chemistry, University of California, Riverside, CA 92521, USA.
Zucai SuoDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
Yinsheng WangDepartment of Chemistry, University of California, Riverside, CA 92521, USA.
University of California, Riverside · USThe Ohio State University · US

Funding

Chemistry and Biology of DNA CarboxyalkylationR01DK082779 · NIDDK · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI WANG, YINSHENG · 2009 to 2016
$3.0M
NIDDK NIH HHS R01 DK082779
6 · The paper itself

Abstract

Metabolic activation of some N-nitroso compounds (NOCs), an important class of DNA damaging agents, can induce the carboxymethylation of nucleobases in DNA. Very little was previously known about how the carboxymethylated DNA lesions perturb DNA replication in human cells. Here, we investigated the effects of five carboxymethylated DNA lesions, i.e. O6-CMdG, N6-CMdA, N4-CMdC, N3-CMdT and O4-CMdT on the efficiency and fidelity of DNA replication in HEK293T human embryonic kidney cells. We found that, while neither N6-CMdA nor N4-CMdC blocked DNA replication or induced mutations, N3-CMdT, O4-CMdT and O6-CMdG moderately blocked DNA replication and induced substantial frequencies of T→A (81%), T→C (68%) and G→A (6.4%) mutations, respectively. In addition, our results revealed that CRISPR-Cas9-mediated depletion of Pol η resulted in significant drops in bypass efficiencies of N4-CMdC and N3-CMdT. Diminution in bypass efficiencies was also observed for N6-CMdA and O6-CMdG upon depletion of Pol κ, and for O6-CMdG upon removal of Pol ζ. Together, our study provided molecular-level insights into the impacts of the carboxymethylated DNA lesions on DNA replication in human cells, revealed the roles of individual translesion synthesis DNA polymerases in bypassing these lesions, and suggested the contributions of O6-CMdG, N3-CMdT and O4-CMdT to the mutations found in p53 gene of human gastrointestinal cancers.

Indexed as

DNA RepairDNA ReplicationBase SequenceCRISPR-Cas SystemsDeoxyadenosinesDeoxycytidineDNADNA AdductsDNA-Binding ProteinsDNA DamageDNA-Directed DNA PolymeraseDNA Polymerase IIGene EditingHEK293 CellsHumansMutationDeoxyadenosinesDeoxycytidineDNADNA AdductsDNA-Binding ProteinsDNA-Directed DNA PolymeraseDNA Polymerase IIN3-carboxymethylthymidineN4-carboxymethyl-2'-deoxycytidineN6-carboxymethyl-2'-deoxyadenosineO4-carboxymethylthymidinePOLE protein, humanPOLK protein, humanPoly-ADP-Ribose Binding ProteinsRad30 proteinREV3L protein, humanThymidineTumor Suppressor Protein p53Y-Family DNA Polymerases

Identifiers

PMID28531304
PMCPMC5499590
OpenAlexW2620361132

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.