Gene essentiality and synthetic lethality in haploid human cells
Gene essentiality and synthetic lethality in haploid human cells
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DOI：
10.1126/science.aac7557
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发表时间：
2015-11-27
期刊：
影响因子：
56.9
通讯作者：
Brummelkamp, Thijn R.
中科院分区：
文献类型：
--
作者：
Blomen, Vincent A.;Majek, Peter;Brummelkamp, Thijn R.
尽管生命所必需的基因已经在不太复杂的模式生物中被鉴定出来，但它们在人类细胞中的阐明却受到技术障碍的阻碍。我们在单倍体人类细胞中使用了广泛的诱变，以确定在培养条件下最佳适应性所需的约2000个基因。为了研究人类细胞中遗传相互作用的原理，我们创建了一个合成致死网络，专注于完全基于突变的分泌途径。这揭示了一种控制高尔基体内平衡的遗传串扰，一种人类寡糖基转移酶复合物的额外亚基，以及一种被病毒劫持的磷脂酰肌醇4-激酶β适配器。合成致死率图与在酵母中进行的观察相似，并为揭示人类细胞生物学各个方面的遗传网络提供了一条前进的道路。
Although the genes essential for life have been identified in less complex model organisms, their elucidation in human cells has been hindered by technical barriers. We used extensive mutagenesis in haploid human cells to identify approximately 2000 genes required for optimal fitness under culture conditions. To study the principles of genetic interactions in human cells, we created a synthetic lethality network focused on the secretory pathway based exclusively on mutations. This revealed a genetic cross-talk governing Golgi homeostasis, an additional subunit of the human oligosaccharyltransferase complex, and a phosphatidylinositol 4-kinase beta adaptor hijacked by viruses. The synthetic lethality map parallels observations made in yeast and projects a route forward to reveal genetic networks in diverse aspects of human cell biology.