AN IMPLANTED RECOMBINATION HOT-SPOT STIMULATES RECOMBINATION AND ENHANCES SISTER-CHROMATID COHESION OF HETEROLOGOUS YACS DURING YEAST MEIOSIS

Heterologous yeast artificial chromosomes (YACs) do not recombine with each other and missegregate in 25% of meiosis I events. Recombination hot spots in the yeast Saccharomyces cerevisiae have previously been shown to be associated with sites of meiosis-induced double-strand bre aks (DSBs). A 6-kb fragment containing a recombination hot spot/DSB si te was implanted onto two heterologous human DNA YACs and was shown to cause the YACs to undergo meiotic recombination in 5-8% of tetrads. R eciprocal exchanges initiated and resolved within the 6-kb insert. Pre sence of the insert had no detectable effect on meiosis I nondisjuncti on. Surprisingly, the recombination hot spots acted in cis to signific antly reduce precocious sister-chromatid segregation. This novel obser vation suggests that DSBs are instrumental in maintaining cohesion bet ween sister chromatids in meiosis I. We propose that this previously u nknown function of DSBs is mediated by the stimulation of sister-chrom atid exchange and/or its intermediates.