The unfolded protein response is required for haploid tolerance in yeast.

HAC1 encodes a transcription factor that mediates the unfolded protein response (UPR) in Saccharomyces cerevisiae. We characterized hac1Delta mutants in the sporulation-proficient SK1 genetic background and found a novel function for HAC1 in haploid tolerance. hac1Delta spore clones contain a diploid DNA content as determined by fluorescence-activated cell sorting and genetic analyses. Autodiploidization of hac1 spore clones occurred after germination; hac1 spores were born haploid, but efficiently generated diploid progeny during the subsequent mitotic division. Once the hac1 mutant acquired a diploid DNA content, no further ploidy increase was observed. Interestingly, the increase in genome content following meiosis was not a general property associated with hac1 spore clones; instead, it was restricted to an inability to tolerate the haploid state. Genetic analyses involving the UPR target gene KAR2 and the UPR regulator IRE1 revealed that autodiploidization associated with hac1 mutants is a consequence of its role in the UPR pathway. Inhibition of the UPR pathway induces autodiploidization, and constitutive activation of UPR target genes suppresses this response.