title: APOBEC3A can activate the DNA damage response and cause cell-cycle arrest.
abstract: Human apolipoprotein-B mRNA-editing catalytic polypeptide-like 3 (APOBEC3) proteins constitute a family of cytidine deaminases that mediate restriction of retroviruses, endogenous retro-elements and DNA viruses. It is well established that these enzymes are potent mutators of viral DNA, but it is unclear whether their editing activity is a threat to the integrity of the cellular genome. We show that expression of APOBEC3A can lead to induction of DNA breaks and activation of damage responses in a deaminase-dependent manner. Consistent with these observations, APOBEC3A expression induces cell-cycle arrest. These results indicate that cellular DNA is vulnerable to APOBEC3 activity and deregulated expression of APOBEC3A could threaten genomic integrity.
authors: Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
authors: Sébastien
authors: S
authors: Landry
authors: Iñigo
authors: I
authors: Narvaiza
authors: Daniel C
authors: DC
authors: Linfesty
authors: Matthew D
authors: MD
authors: Weitzman
mesh_terms: D015153:Blotting, Western; D001973:Bromodeoxyuridine; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D003564:Cytidine Deaminase / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D006657:Histones / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D009709:Nucleotide Deaminases / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D051981:Uracil-DNA Glycosidase / Q000378:metabolism
chemical_list: C468783:H2AX protein, human; D006657:Histones; D011506:Proteins; D051981:Uracil-DNA Glycosidase; D009709:Nucleotide Deaminases; C121399:APOBEC3A protein, human; D003564:Cytidine Deaminase; D001973:Bromodeoxyuridine