Analysis of yeast pms1, msh2, and mlh1 mutators points to differences in mismatch correction efficiencies between prokaryotic and eukaryotic cells.
Genetic stability relies in part on the efficiency with which post-replicative mismatch repair (MMR) detects and corrects DNA replication errors. In Escherichia coli, endogenous transition mispairs and insertion/deletion (ID) heterologies are corrected with similar efficiencies--but much more efficiently than transversion mispairs--as revealed by mutation rate increases in MMR mutants. To assess the relative efficiencies with which these mismatches are corrected in the yeast Saccharomyces cerevisiae, we examined repair of defined mismatches on heteroduplex plasmids and compared the spectra for >1000 spontaneous SUP4-o mutations arising in isogenic wild-type or MMR-deficient (pms1, mlh1, msh2) strains. Heteroduplexes containing G/T mispairs or ID heterologies were corrected more efficiently than those containing transversion mismatches. However, the rates of single base-pair insertion/deletion were increased much more (82-fold or 34-fold, respectively) on average than the rate of base pair substitutions (4.4-fold), with the rates for total transitions and transversions increasing to similar extents. Thus, the relative efficiencies with which mismatches formed during DNA replication are repaired appear to differ in prokaryotic and eukaryotic cells. In addition, our results indicate that in yeast, and probably other eukaryotes, these efficiencies may not mirror those obtained from an analysis of heteroduplex correction.
Atherosclerosis Specialty Laboratory, St. Paul's Hospital, Vancouver, B.C., Canada.
Y
Y
Yang
R
R
Karthikeyan
S E
SE
Mack
E J
EJ
Vonarx
B A
BA
Kunz
D020137:Base Pair Mismatch; D001483:Base Sequence; D002352:Carrier Proteins; D004260:DNA Repair; D004261:DNA Replication; D004251:DNA Transposable Elements; D004271:DNA, Fungal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics; D017354:Point Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion
D002352:Carrier Proteins; D004251:DNA Transposable Elements; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D009692:Nucleic Acid Heteroduplexes; C088858:PMS1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C489751:MSH2 protein, S cerevisiae; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein