Fig. 1. (A) Mating type switching in yeast. Schematic of chromo some III, showing the expressor locus, MAT, the transcriptionally silent donor loci HML and HMR, and the recombination enhancer RE. In MATa cells, Mcm1 binds to the RE and activates HML as donor. In MATα cells, α2 represses the activity of Mcm1 bound to the RE, resulting in use of HMR through an as yet undefined mechanism. (B) Models for the role of chromosome III architecture in mating type switching. Two models could account for donor selection in yeast. Either chromosome III is prefolded in a cell type-specific manner to yield juxtaposition of the preferred donor next to MAT or, following double-strand cleavage, the broken end could physically sample both HML and HMR equally but commit to the preferred donor through, for example, enhanced susceptibility of the preferred donor to strand invasion. The first model would predict that the preferred donor would be located closer to MAT than the non-preferred donor, while the second would predict that no cell type-specific organization of the chromosome would be evident. In this latter case, both donor loci would be either equally unassociated with MAT or equally associated.