The role of protein interactions in mediating essentiality and synthetic lethality.
The role of protein interactions in mediating essentiality and synthetic lethality.
复制标题
蛋白质相互作用在介导本质和合成致死性中的作用。
DOI：
10.1371/journal.pone.0062866
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lovell SC
中科院分区：
文献类型：
--
作者：
Talavera D;Robertson DL;Lovell SC
如果基因的敲除与致死表型相关，则基因被表征为必需的，并且这些“必需基因”在生物学功能中起核心作用。此外，有些基因只有在成对删除时才是必需的，这种现象被称为合成致死。在这里，我们认为基因的合成致死显示为“必要对”的基因，并分析酵母必要基因和合成致死对一起的性质。由于基因复制最初产生一对或一组相同的基因，它经常被用来解释合成致死性。然而，我们发现，复制只解释了少数情况下的合成致命性。同样，代谢途径的破坏导致合成致死的例子相对较少。相比之下，绝大多数合成的致死基因对编码的蛋白质具有共享相互作用伙伴的相关功能。我们还发现必需基因和合成致死对聚集在蛋白质-蛋白质相互作用网络中。这些结果表明，合成致死率强烈依赖于蛋白质-蛋白质相互作用的形成。通过重复的补偿通常不会发生，主要是因为所涉及的基因是最近的重复，但更常见的是由于功能相似性，允许保留必需的蛋白质复合物。这个统一的观点，结合基因是单独的必要与那些形成必要的对，表明必要性是蛋白质之间的物理相互作用蛋白质-蛋白质相互作用的一个特征，而不是基因和蛋白质产物本身固有的。
Genes are characterized as essential if their knockout is associated with a lethal phenotype, and these “essential genes” play a central role in biological function. In addition, some genes are only essential when deleted in pairs, a phenomenon known as synthetic lethality. Here we consider genes displaying synthetic lethality as “essential pairs” of genes, and analyze the properties of yeast essential genes and synthetic lethal pairs together. As gene duplication initially produces an identical pair or sets of genes, it is often invoked as an explanation for synthetic lethality. However, we find that duplication explains only a minority of cases of synthetic lethality. Similarly, disruption of metabolic pathways leads to relatively few examples of synthetic lethality. By contrast, the vast majority of synthetic lethal gene pairs code for proteins with related functions that share interaction partners. We also find that essential genes and synthetic lethal pairs cluster in the protein-protein interaction network. These results suggest that synthetic lethality is strongly dependent on the formation of protein-protein interactions. Compensation by duplicates does not usually occur mainly because the genes involved are recent duplicates, but is more commonly due to functional similarity that permits preservation of essential protein complexes. This unified view, combining genes that are individually essential with those that form essential pairs, suggests that essentiality is a feature of physical interactions between proteins protein-protein interactions, rather than being inherent in gene and protein products themselves.
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影响因子：
--
作者：
Collins, Sean R.;Roguev, Assen;Krogan, Nevan J.
通讯作者：
Krogan, Nevan J.
影响因子：
64.8
作者：
Jeong, H;Mason, SP;Oltvai, ZN
通讯作者：
Oltvai, ZN
在基因组量表上对酵母中适应性和遗传相互作用的定量分析。
影响因子：
48
作者：
Baryshnikova, Anastasia;Costanzo, Michael;Kim, Yungil;Ding, Huiming;Koh, Judice;Toufighi, Kiana;Youn, Ji-Young;Ou, Jiongwen;San Luis, Bryan-Joseph;Bandyopadhyay, Sunayan;Hibbs, Matthew;Hess, David;Gingras, Anne-Claude;Bader, Gary D.;Troyanskaya, Olga G.;Brown, Grant W.;Andrews, Brenda;Boone, Charles;Myers, Chad L.
通讯作者：
Myers, Chad L.
影响因子：
4.5
作者：
He X;Zhang J
通讯作者：
Zhang J
影响因子：
4.3
作者：
Bandyopadhyay S;Kelley R;Krogan NJ;Ideker T
通讯作者：
Ideker T