Evidence map›Paper›PMID 38634780›Full record

ArticleNucleic acids research2024

Biochemical and structural characterization of Fapy•dG replication by Human DNA polymerase β.

Shijun Gao, Peyton N Oden, Benjamin J Ryan, Haozhe Yang, Bret D Freudenthal, Marc M Greenberg

Open access · goldAbstract read
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 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 32% 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, 3 citations in OpenAlex.

  1. Review
  2. Article
  3. 8-OxodGuo and Fapy•dG Mutagenicity inChemical research in toxicology · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Shijun GaoDepartment of Chemistry, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.
Peyton N OdenDepartment of Biochemistry and Molecular Biology, and Department of Cancer Biology, University of Kansas Medical Center, KS City, KS 66160, USA.
Benjamin J RyanDepartment of Biochemistry and Molecular Biology, and Department of Cancer Biology, University of Kansas Medical Center, KS City, KS 66160, USA.
Haozhe YangDepartment of Chemistry, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.
Bret D FreudenthalDepartment of Biochemistry and Molecular Biology, and Department of Cancer Biology, University of Kansas Medical Center, KS City, KS 66160, USA.ORCID 0000-0003-1449-4710
Marc M GreenbergDepartment of Chemistry, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.ORCID 0000-0002-5786-6118
Johns Hopkins University · USThe University of Kansas Cancer Center · US

Funding

How Damaged DNA Forms, and its Subsequent Chemistry: Fundamental Studies and ApplicationsR35GM131736 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI MARC M GREENBERG · 2019 to 2026
$4.3M
Supplement to NIH Award 2 R35GM128562-06R35GM128562 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Bret D Freudenthal · 2018 to 2026
$4.2M
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
Robust and Fast Taq Mutants Designed for Direct and Rapid Point of Care TestsR43GM128532 · NIGMS · DNA POLYMERASE TECHNOLOGY, INC. · PI KERMEKCHIEV, MILKO B · 2018 to 2018
$150k
NIEHS NIH HHS ES-027558NIEHS NIH HHS R01 ES027558NIGMS NIH HHS GM-131736NIGMS NIH HHS R35 GM128562NIGMS NIH HHS R35 GM131736NIGMS NIH HHS R43 GM128532
6 · The paper itself

Abstract

N6-(2-deoxy-α,β-d-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamido-pyrimidine (Fapy•dG) is formed from a common intermediate and in comparable amounts to the well-studied mutagenic DNA lesion 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo). Fapy•dG preferentially gives rise to G → T transversions and G → A transitions. However, the molecular basis by which Fapy•dG is processed by DNA polymerases during this mutagenic process remains poorly understood. To address this we investigated how DNA polymerase β (Pol β), a model mammalian polymerase, bypasses a templating Fapy•dG, inserts Fapy•dGTP, and extends from Fapy•dG at the primer terminus. When Fapy•dG is present in the template, Pol β incorporates TMP less efficiently than either dCMP or dAMP. Kinetic analysis revealed that Fapy•dGTP is a poor substrate but is incorporated ∼3-times more efficiently opposite dA than dC. Extension from Fapy•dG at the 3'-terminus of a nascent primer is inefficient due to the primer terminus being poorly positioned for catalysis. Together these data indicate that mutagenic bypass of Fapy•dG is likely to be the source of the mutagenic effects of the lesion and not Fapy•dGTP. These experiments increase our understanding of the promutagenic effects of Fapy•dG.

Indexed as

DNA Polymerase betaDNA ReplicationFormamidesFuransPyrimidinesCrystallography, X-RayDNAHumansKineticsModels, MolecularMutagenesisDNADNA Polymerase betaFormamidesFuransN6-(2-deoxy-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamidopyrimidinePOLB protein, humanPyrimidines

Identifiers

PMID38634780
PMCPMC11109955
OpenAlexW4394919481

What OpenQuestion holds

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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.