MICROSATELLITE INSTABILITY IN YEAST - DEPENDENCE ON REPEAT UNIT SIZE AND DNA MISMATCH REPAIR GENES

We examined the stability of microsatellites of different repeat unit lengths in Saccharomyces cerevisiae strains deficient in DNA mismatch repair. The msh2 and msh3 mutations destabilized microsatellites with repeat units of 1, 2, 4, 5, and 8 bp; a poly(G) tract of 18 bp was des tabilized several thousand-fold by the msh2 mutation and about 100-fol d by msh3. The msh6 mutations destabilized microsatellites with repeat units of 1 and 2 bp but had no effect on microsatellites with larger repeats. These results argue that coding sequences containing repetiti ve DNA. tracts will be preferred target sites for mutations in human t umors with mismatch repair defects. We find that the DNA mismatch repa ir genes destabilize microsatellites with repeat units from 1 to 13 bp but have no effect on the stability of minisatellites with repeat uni ts of 16 or 20 bp. Our data also suggest that displaced loops on the n ascent strand, resulting from DNA polymerase slippage, are repaired di fferently than loops on the template strand.