Lee Kyungho, Neigeborn Lenore, Kaufman Randal J
Howard Hughes Medical Institute, Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
J Biol Chem. 2003 Apr 4;278(14):11818-27. doi: 10.1074/jbc.M210475200. Epub 2003 Jan 30.
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.
HAC1编码一种转录因子，该转录因子介导酿酒酵母中的未折叠蛋白反应（UPR）。我们在孢子形成能力强的SK1遗传背景中对hac1Delta突变体进行了表征，发现HAC1在单倍体耐受性方面具有新功能。通过荧光激活细胞分选和遗传分析确定，hac1Delta孢子克隆含有二倍体DNA含量。hac1孢子克隆在萌发后发生了自体二倍体化；hac1孢子最初是单倍体，但在随后的有丝分裂过程中有效地产生了二倍体后代。一旦hac1突变体获得了二倍体DNA含量，就没有观察到进一步的倍性增加。有趣的是，减数分裂后基因组含量的增加并非hac1孢子克隆的普遍特性；相反，它仅限于无法耐受单倍体状态。涉及UPR靶基因KAR2和UPR调节因子IRE1的遗传分析表明，与hac1突变体相关的自体二倍体化是其在UPR途径中作用的结果。抑制UPR途径会诱导自体二倍体化，而UPR靶基因的组成型激活会抑制这种反应。
