Removal of frameshift intermediates by mismatch repair proteins in Saccharomyces cerevisiae.
Frameshift mutations occur when the coding region of a gene is altered by addition or deletion of a number of base pairs that is not a multiple of three. The occurrence of a deletion versus an insertion type of frameshift depends on the nature of the transient intermediate structure formed during DNA synthesis. Extrahelical bases on the template strand give rise to deletions, whereas extrahelical bases on the strand being synthesized produce insertions. We previously used reversion of a +1 frameshift mutation to analyze the role of the mismatch repair (MMR) machinery in correcting -1 frameshift intermediates within a defined region of the yeast LYS2 gene. In this study, we have used reversion of a -1 frameshift mutation within the same region of LYS2 to analyze the role of the MMR machinery in the correction of frameshift intermediates that give rise to insertion events. We found that insertion and deletion events occur at similar rates but that the reversion spectra are very different in both the wild-type and MMR-defective backgrounds. In addition, analysis of the +1 spectra revealed novel roles for Msh3p and Msh6p in removing specific types of frameshift intermediates.
Harfe
B D
BD
Department of Biology, Emory University, Atlanta, Georgia 30322, USA.
Jinks-Robertson
S
S
D048868:Adaptor Proteins, Signal Transducing; D000445:Aldehyde Oxidoreductases / Q000235:genetics*; D000483:Alleles; D020137:Base Pair Mismatch; D001483:Base Sequence; D002352:Carrier Proteins; D004260:DNA Repair; D004271:DNA, Fungal; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D016368:Frameshift Mutation; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D050647:L-Aminoadipate-Semialdehyde Dehydrogenase; D008969:Molecular Sequence Data; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein; D000074081:MutS Homolog 3 Protein; D016296:Mutagenesis; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C088859:MLH1 protein, S cerevisiae; C081696:MSH3 protein, S cerevisiae; C098790:MSH6 protein, S cerevisiae; D000074081:MutS Homolog 3 Protein; C088858:PMS1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000445:Aldehyde Oxidoreductases; D050647:L-Aminoadipate-Semialdehyde Dehydrogenase; C489751:MSH2 protein, S cerevisiae; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein