Gene essentiality and synthetic lethality in haploid human cells

被引：595

作者：

Blomen, Vincent A. ^{[1
]}

Majek, Peter ^{[2
]}

Jae, Lucas T. ^{[1
]}

Bigenzahn, Johannes W. ^{[2
]}

Nieuwenhuis, Joppe ^{[1
]}

Staring, Jacqueline ^{[1
]}

Sacco, Roberto ^{[2
]}

van Diemen, Ferdy R. ^{[1
]}

Olk, Nadine ^{[2
]}

Stukalov, Alexey ^{[2
]}

Marceau, Caleb ^{[3
]}

Janssen, Hans ^{[1
]}

Carette, Jan E. ^{[3
]}

Bennett, Keiryn L. ^{[2
]}

Colinge, Jacques ^{[2
,4
]}

Superti-Furga, Giulio ^{[2
,5
]}

Brummelkamp, Thijn R. ^{[1
,2
,6
]}

机构：

[1] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands

[2] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria

[3] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA

[4] Univ Montpellier, Inst Rech Cancerol Montpellier, INSERM, U1194,Inst Reg Canc Montpellier, F-34000 Montpellier, France

[5] Med Univ Vienna, Ctr Physiol & Pharmacol, Vienna, Austria

[6] Canc Genom Ctr CGC Nl, NL-1066 CX Amsterdam, Netherlands

来源：

SCIENCE | 2015年 / 350卷 / 6264期

基金：

奥地利科学基金会; 欧洲研究理事会;

关键词：

SECRETORY PATHWAY; VIRUS ENTRY; YEAST; EXPLORATION; NETWORKS; REPLICATION; MUTANTS; SCREENS; GENOME;

D O I：

10.1126/science.aac7557

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1092 / 1096

页数：6

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