Mating-type switching has evolved on at least three independent occasions in yeasts. S. cerevisiae, K. lactis and S. pombe all have distinct mechanisms for switching. In common for all three species is that cryptic mating type loci act as donors of mating type information, which is copied from the cryptic (non-expressed) loci into the expressed Mating type (MAT) locus. In K. lactis, the mechanism and regulation of switching is only partly understood, motivating further studies of this organism.

We have found that two different proteins mediate switching from MATa to MATα (Kat1) and MATα to MATa (α3) respectively (See figure). Remarkably, both of these proteins are domesticated transposases, linking selfish DNA with mating-type switching. The translation of one of the transposase genes requires a programmed -1 frameshift. Moreover, we have evidence for that this frameshift is important to prevent excessive activation of the transposase and hence that the cell population switches completely to the MATa genotype. The Kat1 transposase generates hairpin-capped breaks in DNA, and we are studying how the cells open and repair this hairpin-capped DSB. We have also found that mating pheromones inhibit switching and we suggest that this is a way for K. lactis to promote outcrossing at the expense of inbreeding.

Model for mating-type switch in K. lactis (A) In MATα cells, binding of Mts1 to two sites close to the L-repeat is important to induce switching. The α3 protein presumably acts at sites flanking the MATα3 gene. The resulting DNA lesions are channeled into a gene conversion pathway, in which the repetitive L- and R-sequences, present also at the HMRa locus, act as blocks of homology to resolve the recombination intermediates. (B) In MATa cells, Mts1 binds to several sites in the MATa1- MATa2 intergenic region. Kat1 generates a hairpin-capped DNA double strand break (DSB). The hairpin is opened and the DSB induces a gene conversion using the HMLα locus as donor sequence.

 

Through database mining and large scale sequencing efforts we have obtained the genome sequence of four yeast species (K. aestuarii, K.dobzhanskii, K. marxianus and K. wickerhamii) that are the closest known relatives of K. lactis. This enables us to use comparative genomics to learn more about the mechanism and regulation of mating-type switching.

Links

Saccharomyces genome database – a comprehensive knowledge base of Baker’s yeast http://www.yeastgenome.org/

Genolevures a site for genomic exploration of other ascomycetes http://www.genolevures.org/

An excellent lecture on DNA repair/recombination
http://www.youtube.com/watch?v=UzXcq2h0VCk