Saccharomyces cerevisiae donor preference during mating-type switching is dependent on chromosome architecture and organization.

Saccharomyces mating-type (MAT) switching occurs by gene conversion using one of two donors, HMLalpha and HMRa, located near the ends of the same chromosome. MATa cells preferentially choose HMLalpha, a decision that depends on the recombination enhancer (RE) that controls recombination along the left arm of chromosome III (III-L). When RE is inactive, the two chromosome arms constitute separate domains inaccessible to each other; thus HMRa, located on the same arm as MAT, becomes the default donor. Activation of RE increases HMLalpha usage, even when RE is moved 50 kb closer to the centromere. If MAT is inserted into the same domain as HML, RE plays little or no role in activating HML, thus ruling out any role for RE in remodeling the silent chromatin of HML in regulating donor preference. When the donors MAT and RE are moved to chromosome V, RE increases HML usage, but the inaccessibility of HML without RE apparently depends on other chromosome III-specific sequences. Similar conclusions were reached when RE was placed adjacent to leu2 or arg4 sequences engaged in spontaneous recombination. We propose that RE's targets are anchor sites that tether chromosome III-L in MATalpha cells thus reducing its mobility in the nucleus.