Yeast chromosome rearrangements in response to a double-strand break

DNA double-strand breaks can lead to chromosome rearrangements if repaired incorrectly. Such rearrangements occur in cancer cells and can lead to inherited or spontaneous genetic disease. We have found that deletion of the DNA repair protein Rad51 in yeast leads to an increase in chromosome rearrangements. To understand the nature of these rearrangements, we have sequenced the genomes of twelve independent strains lacking Rad51, all of which incurred a rearrangement following induction of a double-strand break on the left arm of chromosome IX. Our analysis indicates that Rad51 normally inhibits a type of repair called single-strand annealing between very short (15-17) nucleotide repeats. This work will help elucidate mechanisms controlling genome stability.