Breeden L, Mikesell G E
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Genes Dev. 1991 Jul;5(7):1183-90. doi: 10.1101/gad.5.7.1183.
Expression of the HO endonuclease triggers mating-type switching in Saccharomyces cerevisiae. Transcription of the HO gene is start-dependent and restricted to the late G1/early S phase of haploid mother cells. The HO promoter contains 10 copies of a cell cycle-regulated upstream activation sequence, which is activated by SWI4 and SWI6. SWI4 mRNA levels vary at least 10-fold throughout the cell cycle and rise sharply just before the rise in HO mRNA levels. Constitutive synthesis of SWI4 mRNA leads to constitutive synthesis of HO mRNA. These data suggest that the cell cycle regulation of SWI4 mRNA is required for the tight cell cycle regulation of HO transcription. High-level constitutive synthesis of SWI4 also suppresses swi5 and swi6 mutations, suggesting that SWI4 is the predominant activator of HO transcription and that mutations in negative regulators of SWI4 could be isolated as suppressors of swi6 mutations. One recessive suppressor of swi6 (ssx1-1) that allowed high-level expression of SWI4 during alpha-factor arrest and constitutive expression of both SWI4 and HO after release from the arrest was isolated. This result suggests that SSX1 has a negative regulatory role in the cell-cycle regulation of SWI4 mRNA accumulation.
HO核酸内切酶的表达会引发酿酒酵母中的交配型转换。HO基因的转录起始依赖且仅限于单倍体母细胞的G1晚期/S期早期。HO启动子包含10个细胞周期调控的上游激活序列拷贝，其由SWI4和SWI6激活。SWI4 mRNA水平在整个细胞周期中至少变化10倍，并在HO mRNA水平升高之前急剧上升。SWI4 mRNA的组成型合成导致HO mRNA的组成型合成。这些数据表明，SWI4 mRNA的细胞周期调控是HO转录严格细胞周期调控所必需的。SWI4的高水平组成型合成也抑制了swi5和swi6突变，这表明SWI4是HO转录的主要激活因子，并且SWI4负调控因子的突变可以作为swi6突变的抑制子被分离出来。分离出了一个swi6的隐性抑制子（ssx1-1），它在α因子阻滞期间允许SWI4的高水平表达，并在从阻滞中释放后允许SWI4和HO的组成型表达。该结果表明SSX1在SWI4 mRNA积累的细胞周期调控中具有负调控作用。
