APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast

April J. Schumacher, Dwight V. Nissley, Reuben S. Harris

Research output: Contribution to journalArticlepeer-review

126 Scopus citations


Human cells harbor a variety of factors that function to block the proliferation of foreign nucleic acid. The APOBEC3G enzyme inhibits the replication of retroviruses by deaminating nascent retroviral cDNA cytosines to uracils, lesions that can result in lethal levels of hypermutation. Here, we demonstrate that APOBEC3G is capable of deaminating genomic cytosines in Saccharomyces cerevisiae. APOBEC3G expression caused a 20-fold increase in frequency of mutation to canavanine-resistance, which was further elevated in a uracil DNA glycosylase-deficient background. All APOBEC3G-induced base substitution mutations mapped to the nuclear CAN1 gene and were exclusively C/G → T/A transition mutations within a 5′-CC consensus. The APOBEC3G preferred sites were found on both strands of the DNA duplex, but were otherwise located in hotspots nearly identical to those found previously in retroviral cDNA. This unique genetic system further enabled us to show that expression of APOBEC3G or its homolog APOBEC3F was able to inhibit the mobility of the retrotransposon Ty1 by a mechanism that involves the deamination of cDNA cytosines. Thus, these data expand the range of likely APOBEC3 targets to include nuclear DNA and endogenous retroelements, which have pathological and physiological implications, respectively. We postulate that the APOBECB-dependent innate cellular defense constitutes a tightly regulated arm of a conserved mobile nucleic acid restriction mechanism that is poised to limit internal as well as external assaults.

Original languageEnglish (US)
Pages (from-to)9854-9859
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number28
StatePublished - Jul 12 2005
Externally publishedYes


  • Cytodeamination
  • Endogenous retrotransposon Ty1
  • Hypermutation
  • Saccharomyces cerevisiae

ASJC Scopus subject areas

  • General


Dive into the research topics of 'APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast'. Together they form a unique fingerprint.

Cite this