Expansions and Contractions in a Tandem Repeat Induced by Double-Strand Break Repair

ABSTRACT

Repair of a double-strand break (DSB) in yeast can induce very frequent expansions and contractions in a tandem array of 375-bp repeats. These results strongly suggest that DSB repair can be a major source of amplification of tandemly repeated sequences. Most of the DSB repair events are not associated with crossover. Rearrangements appear in 50% of these repaired recipient molecules. In contrast, the donor template nearly always remains unchanged. Among the rare crossover events, similar rearrangements are found. These results cannot readily be explained by the gap repair model of Szostak et al. (J. W. Szostak, T. L. Orr-Weaver, R. J. Rothstein, and F. W. Stahl, Cell 33:25–35, 1983) but can be explained by synthesis-dependent strand annealing (SDSA) models that allow for crossover. Support for SDSA models is provided by a demonstration that a single DSB repair event can use two donor templates located on two different chromosomes.

ACKNOWLEDGMENTS

We thank Susan Lovett, Michael Lichten, and members of the Haber laboratory for their helpful comments on the manuscript.

This work was supported by National Institutes of Health grant GM20056. F.P. was a fellow of the Association pour la Recherche contre le Cancer, and then of the Jane Coffin Childs Memorial Fund for Medical Research.