Efficient deamination of 5-methylcytidine and 5-substituted cytidine residues in DNA by human APOBEC3A cytidine deaminase

PLoS One. 2013 Jun 20;8(6):e63461. doi: 10.1371/journal.pone.0063461. Print 2013.

Abstract

Deamination of 5-methylcytidine (5MeC) in DNA results in a G:T mismatch unlike cytidine (C) deamination which gives rise to a G:U pair. Deamination of C was generally considered to arise spontaneously. It is now clear that human APOBEC3A (A3A), a polynucleotide cytidine deaminase (PCD) with specificity for single stranded DNA, can extensively deaminate human nuclear DNA. It is shown here that A3A among all human PCDs can deaminate 5-methylcytidine in a variety of single stranded DNA substrates both in vitro and in transfected cells almost as efficiently as cytidine itself. This ability of A3A to accommodate 5-methyl moiety extends to other small and physiologically relevant substituted cytidine bases such as 5-hydroxy and 5-bromocytidine. As 5MeCpG deamination hotspots characterize many genes associated with cancer it is plausible that A3A is a major player in the onset of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • CpG Islands
  • Cytidine / analogs & derivatives*
  • Cytidine / chemistry
  • Cytidine / metabolism
  • Cytidine Deaminase / chemistry*
  • Cytidine Deaminase / metabolism
  • DNA, Single-Stranded / chemistry*
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • Deamination
  • Genes, p53
  • HEK293 Cells
  • HIV-1 / genetics
  • Humans
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Proteins / chemistry*
  • Proteins / metabolism
  • Quail
  • Substrate Specificity

Substances

  • DNA, Single-Stranded
  • DNA, Viral
  • Oligodeoxyribonucleotides
  • Proteins
  • Cytidine
  • APOBEC3A protein, human
  • Cytidine Deaminase
  • 5-methylcytidine

Grant support

The work was supported by grants from Institut Pasteur and the CNRS. The Molecular Retrovirology Unit is équipe labellisée par la Ligue pour la Recherche contre le Cancer. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.