Exclusive induction of G:C to A:T transitions by 3-azido-1,2-propanediol in yeast

Mutat Res Genet Toxicol Environ Mutagen. 2014 Jan 15:760:73-6. doi: 10.1016/j.mrgentox.2013.10.006. Epub 2013 Nov 5.

Abstract

Sodium azide is a strong mutagen which has been successfully employed in mutation breeding of crop plants. In biological systems, it is metabolized to azidoalanine, but further bioactivation to a putative ultimate mutagen as well as the nature of the induced DNA modifications leading to mutations remain elusive. In this study, mutations induced in the CAN1 gene of yeast Saccharomyces cerevisiae by the representative mutagen 3-azido-1,2-propanediol (azidoglycerol, AZG) have been sequenced. Analysis of the forward mutation spectrum to canavanine resistance revealed that AZG induced nearly exclusively G:C to A:T transitions. AZG also induced reversions to tryptophan prototrophy by base-pair substitutions in a dose-dependent manner. This unusual mutational specificity may be shared by other organic azido compounds.

Keywords: Azide; Mutagenesis; Yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems, Basic / genetics
  • Azides / pharmacology*
  • Canavanine / pharmacology
  • DNA Mutational Analysis
  • Dose-Response Relationship, Drug
  • Drug Resistance, Fungal / genetics
  • Mutagenesis / drug effects*
  • Mutation / drug effects*
  • Propylene Glycols / pharmacology*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae Proteins / genetics
  • Tryptophan / pharmacology

Substances

  • Amino Acid Transport Systems, Basic
  • Azides
  • CAN1 protein, S cerevisiae
  • Propylene Glycols
  • Saccharomyces cerevisiae Proteins
  • Canavanine
  • azidoglycerol
  • Tryptophan