Systematic pathway analysis using high-resolution fitness profiling of combinatorial gene deletions
Systematic pathway analysis using high-resolution fitness profiling of combinatorial gene deletions
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DOI：
10.1038/ng1948
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发表时间：
2007-02-01
期刊：
影响因子：
30.8
通讯作者：
Giaever, Guri
中科院分区：
文献类型：
--
作者：
St Onge, Robert P.;Mani, Ramamurthy;Giaever, Guri
系统的遗传相互作用研究阐明了许多细胞过程。在这里，我们定量研究了26个酿酒酵母基因之间的遗传相互作用，赋予耐DNA损伤剂甲磺酸甲酯（MMS），确定合并缺失菌株的化学基因组适应性分析。我们构建了650个双缺失菌株，对应于这26个缺失的所有配对。在存在和不存在MMS的情况下测量单缺失和双缺失菌株的适合度。遗传相互作用是通过结合统计学和经典遗传学的原理来定义的。由此产生的网络预测Mph1解旋酶在解析同源重组衍生的DNA中间体中具有与Sgs1解旋酶相似（但不同）的作用。我们的研究结果强调了小分子和多因子缺失突变体在揭示功能关系和途径顺序中的效用。
Systematic genetic interaction studies have illuminated many cellular processes. Here we quantitatively examine genetic interactions among 26 Saccharomyces cerevisiae genes conferring resistance to the DNA- damaging agent methyl methanesulfonate ( MMS), as determined by chemogenomic fitness profiling of pooled deletion strains. We constructed 650 double- deletion strains, corresponding to all pairings of these 26 deletions. The fitness of single- and double- deletion strains were measured in the presence and absence of MMS. Genetic interactions were defined by combining principles from both statistical and classical genetics. The resulting network predicts that the Mph1 helicase has a role in resolving homologous recombination - derived DNA intermediates that is similar to ( but distinct from) that of the Sgs1 helicase. Our results emphasize the utility of small molecules and multifactorial deletion mutants in uncovering functional relationships and pathway order.