Tfs1, transcription elongation factor TFIIS, has an impact on chromosome segregation affected by pka1 deletion in Schizosaccharomyces pombe
Tfs1, transcription elongation factor TFIIS, has an impact on chromosome segregation affected by pka1 deletion in Schizosaccharomyces pombe
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Tfs1（转录延伸因子 TFIIS）对粟酒裂殖酵母中 pka1 缺失影响的染色体分离有影响
DOI：
10.1007/s00294-023-01268-0
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发表时间：
2023
期刊：
影响因子：
2.5
通讯作者：
Matsuo Yasuhiro
中科院分区：
文献类型：
--
作者：
Takenaka Kouhei;Nishioka Shiho;Nishida Yuki;Kawamukai Makoto;Matsuo Yasuhiro
粟酒裂殖酵母中cAMP依赖的蛋白激酶（PKA）途径在微管组织和染色体分离中起重要作用。通常，功能性Pka 1的丧失诱导对微管去稳定化药物噻苯咪唑（TBZ）的敏感性和染色体错误分离。为了确定Pka 1参与这些事件的机制，我们通过创建pka 1和102个编码转录因子的单个基因的双缺失菌株来探索转录因子的相关性。发现rst 2 β、tfs 1 β、mca 1 β和moc 3 β对pka 1 β的TBZ敏感表型有抑制作用，其中tfs 1 β的抑制作用最强。所有的单突变体（rst 2 β，tfs 1 β，mca 1 β和moc 3 β）都表现出耐TBZ的表型。Tfs 1具有两个转录结构域（TFIIS和Zn finger结构域），这两个结构域都有助于抑制pka 1 β诱导的TBZ敏感表型。在TBZ存在下，Tfs 1 β可以挽救pka 1 β诱导的染色体错误分离。然而，Tfs 1的表达水平并没有不同的野生型和pka 1 GFP菌株，Tfs 1-GFP蛋白定位于细胞核和细胞质中的两个菌株，这排除了直接调节的表达和定位的Tfs 1的Pka 1。TBZ在pka 1菌株中的生长抑制显著地通过rst 2和tfs 1的双缺失而不是rst 2或tfs 1的单缺失来挽救，表明Rst 2和tfs 1独立地有助于抵消TBZ毒性。我们的研究结果强调Tfs 1作为一个关键的转录因子正确的染色体分离。
The cAMP-dependent protein kinase (PKA) pathway inSchizosaccharomyces pombeplays an important role in microtubule organization and chromosome segregation. Typically, loss of functional Pka1 induces sensitivity to the microtubule-destabilizing drug thiabendazole (TBZ) and chromosome mis-segregation. To determine the mechanism via which Pka1 is involved in these events, we explored the relevance of transcription factors by creating a double-deletion strain ofpka1and 102 individual genes encoding transcription factors. We found thatrst2∆,tfs1∆,mca1∆, andmoc3∆suppressed the TBZ-sensitive phenotype of thepka1∆strain, among whichtfs1∆was the strongest suppressor. All single mutants (rst2∆,tfs1∆,mca1∆, andmoc3∆) showed a TBZ-tolerant phenotype. Tfs1 has two transcriptional domains (TFIIS and Zn finger domains), both of which contributed to the suppression of thepka1∆-induced TBZ-sensitive phenotype.pka1∆-induced chromosome mis-segregation was rescued bytfs1∆in the presence of TBZ.tfs1overexpression induced the TBZ-sensitive phenotype and a high frequency of chromosome mis-segregation, suggesting that the amount of Tfs1 must be strictly controlled. However, Tfs1-expression levels did not differ between the wild-type andpka1∆strains, and the Tfs1-GFP protein was localized to the nucleus and cytoplasm in both strains, which excludes the direct regulation of expression and localization of Tfs1 by Pka1. Growth inhibition by TBZ inpka1∆strains was notably rescued by double deletion ofrst2andtfs1rather than single deletion ofrst2ortfs1, indicating that Rst2 and Tfs1 contribute independently to counteract TBZ toxicity. Our findings highlight Tfs1 as a key transcription factor for proper chromosome segregation.
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DOI：
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