Evidence map›Paper›PMID 28472485›Full record

ArticleNucleic acids research2017

APOBEC3A efficiently deaminates methylated, but not TET-oxidized, cytosine bases in DNA.

Emily K Schutsky, Christopher S Nabel, Amy K F Davis, Jamie E DeNizio, Rahul M Kohli

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 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

57 citing papers in PubMed, 90 citations in OpenAlex.

  1. Article
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  4. HAMMER: Hairpin-based APOBEC3A-mediated mRNA editing reporter.bioRxiv : the preprint server for biology · 2026
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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

5 authors at 1 institution in 1 country.

Emily K SchutskyDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Christopher S NabelDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Amy K F DavisDepartment of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jamie E DeNizioDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Rahul M KohliDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
University of Pennsylvania · US

Funding

TRAINING PROGRAM IN CELL AND MOLECULAR BIOLOGYT32GM007229 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BARTOLOMEI, MARISA S. · 1985 to 2023
$14.0M
The mechanism and modulation of 5-methylcytosine oxidation by TET family enzymesR01GM118501 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI KOHLI, RAHUL MANU · 2017 to 2020
$1.2M
NIGMS NIH HHS R01 GM118501NIGMS NIH HHS T32 GM007229
6 · The paper itself

Abstract

AID/APOBEC family enzymes are best known for deaminating cytosine bases to uracil in single-stranded DNA, with characteristic sequence preferences that can produce mutational signatures in targets such as retroviral and cancer cell genomes. These deaminases have also been proposed to function in DNA demethylation via deamination of either 5-methylcytosine (mC) or TET-oxidized mC bases (ox-mCs), which include 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. One specific family member, APOBEC3A (A3A), has been shown to readily deaminate mC, raising the prospect of broader activity on ox-mCs. To investigate this claim, we developed a novel assay that allows for parallel profiling of activity on all modified cytosines. Our steady-state kinetic analysis reveals that A3A discriminates against all ox-mCs by >3700-fold, arguing that ox-mC deamination does not contribute substantially to demethylation. A3A is, by contrast, highly proficient at C/mC deamination. Under conditions of excess enzyme, C/mC bases can be deaminated to completion in long DNA segments, regardless of sequence context. Interestingly, under limiting A3A, the sequence preferences observed with targeting unmodified cytosine are further exaggerated when deaminating mC. Our study informs how methylation, oxidation, and deamination can interplay in the genome and suggests A3A's potential utility as a biotechnological tool to discriminate between cytosine modification states.

Indexed as

5-MethylcytosineBase SequenceCytidine DeaminaseCytosineDNADNA MethylationHumansIn Vitro TechniquesKineticsModels, BiologicalOxidation-ReductionProteinsRecombinant ProteinsSubstrate Specificity5-MethylcytosineAPOBEC3A protein, humanCytidine DeaminaseCytosineDNAProteinsRecombinant Proteins

Identifiers

PMID28472485
PMCPMC5570014
OpenAlexW2610986140

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.