系统三重突变分析揭示了参与染色体调控的途径之间的功能连接。
Systematic triple-mutant analysis uncovers functional connectivity between pathways involved in chromosome regulation.
机构信息
Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Waltham, MA 02454, USA.
出版信息
Cell Rep. 2013 Jun 27;3(6):2168-78. doi: 10.1016/j.celrep.2013.05.007. Epub 2013 Jun 6.
Abstract
Genetic interactions reveal the functional relationships between pairs of genes. In this study, we describe a method for the systematic generation and quantitation of triple mutants, termed triple-mutant analysis (TMA). We have used this approach to interrogate partially redundant pairs of genes in S. cerevisiae, including ASF1 and CAC1, two histone chaperones. After subjecting asf1Δ cac1Δ to TMA, we found that the Swi/Snf Rdh54 protein compensates for the absence of Asf1 and Cac1. Rdh54 more strongly associates with the chromatin apparatus and the pericentromeric region in the double mutant. Moreover, Asf1 is responsible for the synthetic lethality observed in cac1Δ strains lacking the HIRA-like proteins. A similar TMA was carried out after deleting both CLB5 and CLB6, cyclins that regulate DNA replication, revealing a strong functional connection to chromosome segregation. This approach can reveal functional redundancies that cannot be uncovered through traditional double-mutant analyses.
摘要
遗传相互作用揭示了基因对之间的功能关系。在这项研究中，我们描述了一种系统产生和定量三突变体的方法，称为三突变体分析（TMA）。我们已经使用这种方法研究了酿酒酵母中部分冗余的基因对，包括两个组蛋白伴侣 ASF1 和 CAC1。在对 asf1Δ cac1Δ进行 TMA 后，我们发现 Swi/Snf Rdh54 蛋白可以弥补 Asf1 和 Cac1 的缺失。Rdh54 与染色质装置和着丝粒区域的结合更强。此外，Asf1 负责在缺乏 HIRA 样蛋白的 cac1Δ 菌株中观察到的合成致死性。在删除调节 DNA 复制的 cyclin CLB5 和 CLB6 后，也进行了类似的 TMA，揭示了与染色体分离的强烈功能联系。这种方法可以揭示通过传统的双突变分析无法揭示的功能冗余。
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