Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map
Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map
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DOI：
10.1038/nature05649
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发表时间：
2007-04-12
期刊：
影响因子：
64.8
通讯作者：
Krogan, Nevan J.
中科院分区：
文献类型：
--
作者：
Collins, Sean R.;Miller, Kyle M.;Krogan, Nevan J.
定义蛋白质之间的功能关系对于理解细胞生物学的几乎所有方面都至关重要。蛋白质复合物的大规模鉴定为实现这一目标迈出了重要的一步；然而，即使了解每种蛋白质-蛋白质相互作用的化学计量、亲和力和寿命也无法揭示此类复合物之间和内部的功能关系。遗传相互作用可以提供蛋白质-蛋白质相互作用数据集基本上不可见的功能信息。在这里，我们提出了一个上位微阵列图谱 (E-MAP)(1)，该图谱由涉及染色体生物学各个方面（包括 DNA 复制/修复、染色单体分离和转录调控）的 743 个酿酒酵母基因之间的遗传相互作用的定量成对测量组成。该电子地图揭示了物理相互作用分为两个典型的类别，根据各个蛋白质是否一致地行动来执行共同的功能来区分。因此，遗传相互作用数据使得能够在功能上剖析包括介体在内的多蛋白复合物，并将不同的蛋白复合物组织成通路。在此处定义的一条通路中，我们表明 Rtt109 是一类新型组蛋白乙酰转移酶的创始成员，负责组蛋白 H3 在赖氨酸 56 上的 Asf1 依赖性乙酰化。这种修饰反过来使包含 cullin Rtt101 的泛素连接酶复合物能够确保 DNA 复制过程中的基因组完整性。
Defining the functional relationships between proteins is critical for understanding virtually all aspects of cell biology. Large-scale identification of protein complexes has provided one important step towards this goal; however, even knowledge of the stoichiometry, affinity and lifetime of every protein - protein interaction would not reveal the functional relationships between and within such complexes. Genetic interactions can provide functional information that is largely invisible to protein - protein interaction data sets. Here we present an epistatic miniarray profile (E-MAP)(1) consisting of quantitative pairwise measurements of the genetic interactions between 743 Saccharomyces cerevisiae genes involved in various aspects of chromosome biology ( including DNA replication/ repair, chromatid segregation and transcriptional regulation). This E-MAP reveals that physical interactions fall into two well-represented classes distinguished by whether or not the individual proteins act coherently to carry out a common function. Thus, genetic interaction data make it possible to dissect functionally multi-protein complexes, including Mediator, and to organize distinct protein complexes into pathways. In one pathway defined here, we show that Rtt109 is the founding member of a novel class of histone acetyltransferases responsible for Asf1-dependent acetylation of histone H3 on lysine 56. This modification, in turn, enables a ubiquitin ligase complex containing the cullin Rtt101 to ensure genomic integrity during DNA replication.