Mapping the polarity of changes that occur in interrupted CAG repeat tracts in yeast

To explore the mechanismsby which CAG trinucleotide repeat tracts undergo length changes in yeast cells, we examined the polarity of alterations with respect to an interrupting CAT trinucleotide near the center of the tract. In wild-type cells, in which most tract changes are large contractions, the changes that retain the interruption are biased toward the 3' end of the repeat tract (in reference to the direction of lagging-strand synthesis). In rth1/rad27 mutant cells that are defective in Okazaki fragment maturation, the tract expansions are biased to the 5' end of the repeat tract, while the tract contractions that do not remove the interruption occur randomly on either side of the interruption. In msh2 mutant cells that are defective in the mismatch repair machinery, neither the small changes of one or two repeat units nor the larger contractions attributable to this mutation are biased to either side of the interruption. The results of this study are discussed in terms of the molecular paths leading to expansions and contractions of repeat tracts.