Evidence map›Paper›PMID 34464900›Full record

ArticleDNA repair2021

Sequence context effects of replication of Fapy•dG in three mutational hot spot sequences of the p53 gene in human cells.

Jan Henric T Bacurio, Haozhe Yang, Spandana Naldiga, Brent V Powell, Benjamin J Ryan, Bret D Freudenthal, Marc M Greenberg, Ashis K Basu

Open access · greenAbstract read
In one paragraph

Article in DNA repair, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

12 citing papers in PubMed, 15 citations in OpenAlex.

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  12. Beyond the Lesion: Back to High Fidelity DNA Synthesis.Frontiers in molecular biosciences · 2021
    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

8 authors at 3 institutions in 1 country.

Jan Henric T BacurioDepartment of Chemistry, University of Connecticut, Storrs, CT, 06269, USA.
Haozhe YangDepartment of Chemistry, Johns Hopkins University, Baltimore, MD, 21218, USA.
Spandana NaldigaDepartment of Chemistry, University of Connecticut, Storrs, CT, 06269, USA.
Brent V PowellDepartment of Chemistry, University of Connecticut, Storrs, CT, 06269, USA.
Benjamin J RyanDepartment of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
Bret D FreudenthalDepartment of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
Marc M GreenbergDepartment of Chemistry, Johns Hopkins University, Baltimore, MD, 21218, USA. Electronic address: mgreenberg@jhu.edu.
Ashis K BasuDepartment of Chemistry, University of Connecticut, Storrs, CT, 06269, USA. Electronic address: ashis.basu@uconn.edu.
University of Connecticut · USJohns Hopkins University · USUniversity of Kansas Medical Center · US

Funding

Biochemical studies on Fapy-dG with eukaryotic enzymes and in mammalian cellsR01ES027558 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI GREENBERG, MARC M · 2017 to 2021
$1.7M
NIEHS NIH HHS R01 ES027558
6 · The paper itself

Abstract

Fapy•dG and 8-OxodGuo are formed in DNA from a common N7-dG radical intermediate by reaction with hydroxyl radical. Although cellular levels of Fapy•dG are often greater, its effects on replication are less well understood than those of 8-OxodGuo. In this study plasmid DNA containing Fapy•dG in three mutational hotspots of human cancers, codons 248, 249, and 273 of the p53 tumor suppressor gene, was replicated in HEK 293T cells. TLS efficiencies for the Fapy•dG containing plasmids varied from 72 to 89%, and were further reduced in polymerase-deficient cells. The mutation frequency (MF) of Fapy•dG ranged from 7.3 to 11.6%, with G→T and G→A as major mutations in codons 248 and 249 compared to primarily G→T in codon 273. Increased MF in hPol ι-, hPol κ-, and hPol ζ-deficient cells suggested that these polymerases more frequently insert the correct nucleotide dC opposite Fapy•dG, whereas decreased G→A in codons 248 and 249 and reduction of all mutations in codon 273 in hPol λ-deficient cells indicated hPol λ's involvement in Fapy•dG mutagenesis. In vitro kinetic analysis using isolated translesion synthesis polymerases and hPol λ incompletely corroborated the mutagenesis experiments, indicating codependence on other proteins in the cellular milieu. In conclusion, Fapy•dG mutagenesis is dependent on the DNA sequence context, but its bypass by the TLS polymerases is largely error-free.

Indexed as

DNA AdductsFormamidesFuransGenes, p53PyrimidinesDNA DamageDNA ReplicationHumansKineticsMutationTumor Suppressor Protein p53DNA AdductsFormamidesFuransN6-(2-deoxy-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamidopyrimidinePyrimidinesTP53 protein, humanTumor Suppressor Protein p532ʹ-deoxyguanosine lesionMutagenesisOxidative DNA damagePolymerase knockoutTranslesion synthesis

Identifiers

PMID34464900
PMCPMC8616820
OpenAlexW3194182718

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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.