The DNA damage induced by the Cytosine Deaminase APOBEC3A Leads to the production of ROS

Human apolipoprotein B mRNA-editing catalytic polypeptide-like 3 proteins (APOBEC3s or A3s) are cytosine deaminases that protect cells by introducing promutagenic uraciles in invading retro-elements. However as a drawback of this protective activity, A3s can also target cellular DNA, leading to DNA...

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Bibliographic Details
Published in:Scientific reports 2019-03, Vol.9 (1), p.4714, Article 4714
Main Authors: Niocel, Mathilde, Appourchaux, Romain, Nguyen, Xuan-Nhi, Delpeuch, Mathilde, Cimarelli, Andrea
Format: Article
Language:English
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Apolipoprotein B
Biochemistry, Molecular Biology
Cancer
Carcinogenesis - genetics
Carcinogenesis - immunology
Cytidine Deaminase - genetics
Cytidine Deaminase - metabolism
Cytosine
Cytosine deaminase
Deoxyribonucleic acid
DNA
DNA biosynthesis
DNA Damage
Editing
Genomics
HeLa Cells
Humanities and Social Sciences
Humans
Inflammation
Life Sciences
mRNA
multidisciplinary
Mutation
NADPH Oxidases - metabolism
Oxidative Stress - genetics
Oxidative Stress - immunology
Plasmids - genetics
Primary Cell Culture
Proteins - genetics
Proteins - metabolism
Reactive oxygen species
Reactive Oxygen Species - metabolism
RNA editing
Science
Science (multidisciplinary)
Transfection
Tumorigenesis
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Summary:Human apolipoprotein B mRNA-editing catalytic polypeptide-like 3 proteins (APOBEC3s or A3s) are cytosine deaminases that protect cells by introducing promutagenic uraciles in invading retro-elements. However as a drawback of this protective activity, A3s can also target cellular DNA, leading to DNA damage and to the accumulation of somatic mutations that may contribute to tumorigenesis. Among A3s, A3A has been shown to be particularly proficient at mutagenizing cellular DNA, but whether this enzyme exerts additional effects on the cellular physiology remains unclear. Here, we show that A3A editing of cellular DNA leads to reactive oxygen species (ROS) production through Nox-enzymes. ROS production occurs in two distinct model cell lines and it is contingent upon DNA replication and intact enzymatic properties of A3A. For the first time, our results indicate that the editing activity of A3A results in the induction of a pro-inflammatory state that may possibly contribute to the constitution of a tumorigenic-prone environment.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-40941-8