The spectrum of APOBEC3 activity: From anti-viral agents to anti-cancer opportunities

DNA Repair (Amst). 2019 Nov:83:102700. doi: 10.1016/j.dnarep.2019.102700. Epub 2019 Sep 13.

Abstract

The APOBEC3 family of cytosine deaminases are part of the innate immune response to viral infection, but also have the capacity to damage cellular DNA. Detection of mutational signatures consistent with APOBEC3 activity, together with elevated APOBEC3 expression in cancer cells, has raised the possibility that these enzymes contribute to oncogenesis. Genome deamination by APOBEC3 enzymes also elicits DNA damage response signaling and presents therapeutic vulnerabilities for cancer cells. Here, we discuss implications of APOBEC3 activity in cancer and the potential to exploit their mutagenic activity for targeted cancer therapies.

Keywords: APOBEC3; Cytosine deaminase; DNA damage response; Mutational patterns; Synthetic lethality.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antiviral Agents / pharmacology*
  • Cytidine Deaminase / genetics
  • Cytidine Deaminase / metabolism*
  • Humans
  • Molecular Targeted Therapy / methods*
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Neoplasms / genetics

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Cytidine Deaminase