Yeast origins establish a strand bias for replicational mutagenesis

Mol Cell. 2002 Jul;10(1):207-13. doi: 10.1016/s1097-2765(02)00567-1.


To determine whether replicational mutagenesis in the yeast genome is influenced by the positions of active origins, a reporter gene was placed in two orientations at multiple locations within a 39,000 bp region of chromosome III possessing two strong origins. The frequency of mutations resulting from misincorporation of adenine opposite 8-hydroxyguanine in one strand and 6-hydroxylaminopurine opposite cytosine in the other strand differed by 3- to 10-fold, depending on the gene orientation and its distance from the origins. The observed patterns indicate that active origins establish a strand bias for mutations that is maintained over thousands of base pairs and results from lower nucleotide selectivity and/or less efficient proofreading or mismatch repair during leading strand DNA replication.

MeSH terms

  • Chromosomes, Fungal / genetics
  • DNA Replication / genetics*
  • DNA, Fungal / biosynthesis*
  • DNA, Fungal / genetics*
  • Mutagenesis / genetics*
  • Mutation, Missense / genetics*
  • Nucleic Acid Conformation
  • Replication Origin / genetics*
  • Saccharomyces cerevisiae / genetics*


  • DNA, Fungal