APOBEC3A can activate the DNA damage response and cause cell-cycle arrest

Sébastien Landry1, Iñigo Narvaiza, Daniel C Linfesty

  • 1Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.

EMBO Reports
|April 5, 2011
PubMed

Insights

The human apolipoprotein-B mRNA-editing catalytic polypeptide-like 3A (APOBEC3A) enzyme can cause DNA breaks and cell cycle arrest. Deregulated APOBEC3A expression may threaten the integrity of the cellular genome.

Area of Science:

  • Molecular Biology
  • Genetics
  • Virology

Background:

  • Human apolipoprotein-B mRNA-editing catalytic polypeptide-like 3 (APOBEC3) proteins are cytidine deaminases with known antiviral and anti-retroviral activity.
  • APOBEC3 enzymes are recognized as potent mutators of viral DNA.
  • The potential impact of APOBEC3 activity on the host cell's own genome integrity remains largely unexplored.

Purpose of the Study:

  • To investigate whether the editing activity of APOBEC3 proteins poses a risk to the stability of the cellular genome.
  • To determine the consequences of APOBEC3A expression on cellular DNA and cell cycle progression.

Main Methods:

  • Expression of APOBEC3A in cellular systems.
  • Assessment of DNA breaks and DNA damage response activation.
  • Analysis of cell-cycle progression.

Main Results:

  • APOBEC3A expression was found to induce DNA breaks in a deaminase-dependent manner.
  • The induction of DNA breaks by APOBEC3A led to the activation of cellular damage responses.
  • APOBEC3A expression resulted in cell-cycle arrest, indicating a significant cellular response to the induced DNA damage.

Conclusions:

  • Cellular DNA is susceptible to the editing activity of APOBEC3 proteins.
  • Aberrant or deregulated expression of APOBEC3A can compromise genomic integrity.
  • APOBEC3A's potential to induce DNA damage highlights a critical aspect of its biological function beyond viral restriction.

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