Additional information about HR was gained by transforming yeast cells with recombinant plasmids that have yeast genes but lack a yeast replicator sequence. Because the plasmids lack a yeast replicator, their yeast genes can only be maintained if they integrate into the yeast genome. Early experiments showed that plasmids integrated into the yeast genome by HR between the yeast gene on the plasmid and the homologous yeast gene in the chromosomal DNA.

    Terry Orr- Weaver, Jack Szostak, and Rodney Rothstein performed experiments with a yeast transforming plasmid that lacks a yeast replicator and is therefore incapable of autonomous replication. The yeast plasmid carried two yeast markers derived from different chromosomal genes. In some experiments, they used a restriction endonuclease to make one double-strand break in one of the two genes and in other experiments they used two restriction endonucleases to make two double-strand breaks in one of the genes, removing an internal sequence and creating a gap. Surprisingly, the broken plasmids transformed at much higher frequencies than the uncut plasmid. Ail of the transformants were the result, of integration of the plasmid into chromosomal DNA. The plasmid was integrated at the homologous gene sequence in the chromosome and, moreover, the gapped plasmid was repaired during the transformation and integration process. These experiments showed that double-strand breaks stimulate HR. This formed the basis for a new HR model.