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Endogenous APOBEC3A DNA cytosine deaminase is cytoplasmic and nongenotoxic

Allison M Land1, Emily K Law, Michael A Carpenter

  • 1Department of Biochemistry, Molecular Biology and Biophysics, Institute for Molecular Virology, Masonic Cancer Center, and Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA.

The Journal of Biological Chemistry
|May 4, 2013
PubMed

Insights

Monocytes control the DNA-editing enzyme APOBEC3A (A3A) by keeping it in the cytoplasm, preventing its toxic effects during immune responses. This mechanism protects cells from A3A-induced genotoxicity.

Area of Science:

  • Molecular Biology
  • Immunology
  • Genetics

Background:

  • APOBEC3A (A3A) is a DNA cytosine deaminase involved in innate immunity.
  • Exogenously expressed A3A is genotoxic, implying regulatory mechanisms in monocytes.

Purpose of the Study:

  • Investigate how monocytic cells regulate endogenous A3A expression and prevent cytotoxicity.
  • Determine the cellular localization of endogenous A3A and its correlation with toxicity.

Main Methods:

  • Induction of endogenous A3A expression using interferon in CD14+ cells and THP-1.
  • Induction of A3A expression using doxycycline in HEK293 cells.
  • Immunofluorescent microscopy to assess A3A cellular localization.

Main Results:

  • Endogenous A3A induced by interferon in monocytic cells showed no significant cytotoxicity.
  • Doxycycline-induced A3A in HEK293 cells caused significant cytotoxicity at lower protein levels.
  • Interferon-stimulated endogenous A3A localized to the cytoplasm in monocytic cells, unlike transfected A3A.

Conclusions:

  • Monocytic cells employ a cytoplasmic retention mechanism to control A3A.
  • This localization mechanism prevents A3A-mediated genotoxicity during innate immune responses.
Keywords:
APOBEC3ACytoplasmic LocalizationDNA Cytosine DeaminationDNA DamageGamma-H2AXGenotoxicityHIVInnate ImmunityInterferonMonocytes

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