Cohesin-independent segregation of sister chromatids in budding yeast.
Cohesin-independent segregation of sister chromatids in budding yeast.
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DOI：
10.1091/mbc.e11-08-0696
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发表时间：
2012-02
影响因子：
3.3
通讯作者：
Koshland D
中科院分区：
文献类型：
--
作者：
Guacci V;Koshland D
ETOC：粘着蛋白的两个方面的不同功能是它的调节乙酰化和它的贡献细胞活力。当Smc 3 p乙酰化是组成性的或不存在时，几乎没有建立任何凝聚力。细胞保持活力，因为Smc 3 p乙酰化和Wpl 1 p调节染色体凝聚，和一个粘着蛋白独立的分离存在。内聚蛋白在姐妹染色单体之间产生内聚，这使得染色体能够形成双极附着到有丝分裂纺锤体并分离。粘着蛋白还在染色体凝聚、转录调节和DNA损伤修复中起作用。在这里，我们分析乙酰化在调节粘附素功能中的作用，以及它如何影响芽殖酵母的活力。先前的研究表明，凝聚力的建立需要Eco 1 p介导的乙酰化的凝聚素亚基Smc 3 p在残基K113。Smc 3 p乙酰化被认为可以通过仅仅缓解Wpl 1 p抑制来促进建立，因为WPL 1的缺失绕过了ECO 1缺失的致死性（eco 1 Δ wpl 1 Δ）。我们发现在Eco 1 Δ wpl 1 Δ细胞中几乎没有建立凝聚力，这表明Eco 1 p的功能超出了拮抗Wpl 1 p的范围。当SMC 3乙酰基模拟物（K113 Q或K112 R、K113 Q）是细胞中唯一的功能性SMC 3时，也不能建立内聚。这些结果表明，Smc 3 p乙酰化水平影响建立。值得注意的是，尽管它们存在严重的内聚缺陷，但eco 1 Δ wpl 1 Δ和smc 3-K112 R，K113 Q菌株是可行的，因为不依赖于内聚蛋白的机制能够实现双极附着和分离。这种替代机制对于smc 3-K113 Q菌株活力是不够的。Smc 3-K113 Q是一个不具有缩合能力的菌株，而Eco 1 Δ wpl 1 Δ和smc 3-K112 R、K113 Q是一个具有缩合能力的菌株。我们认为Smc 3 p乙酰化和Wpl 1 p拮抗调节凝聚素的重要作用，在缩合。
ETOC: Two aspects of cohesin's diverse functions are its regulation by acetylation and its contributions to cell viability. When Smc3p acetylation is constitutive or absent, little if any cohesion is established. Cells remain viable because Smc3p acetylation and Wpl1p regulate chromosome condensation, and a cohesin-independent segregation exists. Cohesin generates cohesion between sister chromatids, which enables chromosomes to form bipolar attachments to the mitotic spindle and segregate. Cohesin also functions in chromosome condensation, transcriptional regulation, and DNA damage repair. Here we analyze the role of acetylation in modulating cohesin functions and how it affects budding yeast viability. Previous studies show that cohesion establishment requires Eco1p-mediated acetylation of the cohesin subunit Smc3p at residue K113. Smc3p acetylation was proposed to promote establishment by merely relieving Wpl1p inhibition because deletion of WPL1 bypasses the lethality of an ECO1 deletion (eco1Δ wpl1Δ). We find that little, if any, cohesion is established in eco1Δ wpl1Δ cells, indicating that Eco1p performs a function beyond antagonizing Wpl1p. Cohesion also fails to be established when SMC3 acetyl-mimics (K113Q or K112R,K113Q) are the sole functional SMC3s in cells. These results suggest that Smc3p acetylation levels affect establishment. It is remarkable that, despite their severe cohesion defect, eco1Δ wpl1Δ and smc3-K112R,K113Q strains are viable because a cohesin-independent mechanism enables bipolar attachment and segregation. This alternative mechanism is insufficient for smc3-K113Q strain viability. Smc3-K113Q is defective for condensation, whereas eco1Δ wpl1Δ and smc3-K112R,K113Q strains are competent for condensation. We suggest that Smc3p acetylation and Wpl1p antagonistically regulate cohesin's essential role in condensation.