$Saccharomyces$ forkhead protein Fkh1 regulates donor preference during mating-type switching through the recombination enhancer

Overview & Synopsis

Saccharomyces mating-type switching results from replacement by gene conversion of the MAT locus with sequences copied from one of two unexpressed donor loci, HML or HMR. MAT a cells recombine with HML α ∼90% of the time, whereas MAT α cells choose HMR a 80%–90% of the time. HML preference in MAT a is controlled by the cis-acting recombination enhancer (RE) that regulates recombination along the entire left arm of chromosome III. Comparison of RE sequences between S. cerevisiae , S. carlsbergensis , and S. bayanus defines four highly conserved regions (A, B, C, and D) within a 270-bp minimum RE. An adjacent E region enhances RE activity. Multimers of region A, D, or E are sufficient to promote selective use of HML . Regions A, D, and E each bind in vivo the transcription activator forkhead proteins Fkh1p and Fkh2p and their associated Ndd1p, although there are no adjacent open reading frames (ORFs). Deletion of FKH1 significantly reduces MAT a's use of HML , as does mutation of the Fkh1/Fkh2-binding sites in a multimer of region A. We conclude that Fkh1p regulates MAT a donor preference through direct interaction with RE.