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

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.