Yeast origins establish a strand bias for replicational mutagenesis.
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.
Pavlov
Youri I
YI
Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Newlon
Carol S
CS
Kunkel
Thomas A
TA
D015825:Chromosomes, Fungal / Q000235:genetics; D004261:DNA Replication / Q000235:genetics*; D004271:DNA, Fungal / Q000096:biosynthesis* / Q000235:genetics*; D016296:Mutagenesis / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D009690:Nucleic Acid Conformation; D018741:Replication Origin / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*
D004271:DNA, Fungal