Gene function prediction from congruent synthetic lethal interactions in yeast
Gene function prediction from congruent synthetic lethal interactions in yeast
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DOI：
10.1038/msb4100034
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发表时间：
2005-01-01
影响因子：
9.9
通讯作者：
Bader, Joel S.
中科院分区：
文献类型：
--
作者：
Ye, Ping;Peyser, Brian D.;Bader, Joel S.
我们预测基因的功能，利用合成的致死基因之间的相互作用无效等位基因在酿酒酵母。表型和蛋白质相互作用的数据表明，合成致死基因对功能的平行或补偿途径。同源基因对，定义为共享合成的致死伙伴，在单一途径分支。我们预测苯菌灵的敏感性和核迁移缺陷使用的一致性，这些表型与直接合成致死率不相关。我们还预测了YLL 049 W是动力蛋白-动力肌动蛋白途径的新成员，并提供了新的支持性实验证据。我们进行了合成致死筛选的平行有丝分裂出口网络（MEN）和Cdc 14早期后期释放所需的细胞周期晚期的途径。合成致死相互作用在这些途径中桥接基因，并且在每个途径中高度一致地连接基因。MEN和Sin 3/Rpd 3组蛋白去乙酰化酶的所有组分之间的合成致死相互作用揭示了Sin 3/Rpd 3在促进有丝分裂退出中与MEN平行的新功能。这些计算机模拟方法可以预测表型和基因功能，适用于酵母中的基因组合成致死筛选和后生动物中的类似RNA干扰筛选。
We predicted gene function using synthetic lethal genetic interactions between null alleles in Saccharomyces cerevisiae. Phenotypic and protein interaction data indicate that synthetic lethal gene pairs function in parallel or compensating pathways. Congruent gene pairs, defined as sharing synthetic lethal partners, are in single pathway branches. We predicted benomyl sensitivity and nuclear migration defects using congruence; these phenotypes were uncorrelated with direct synthetic lethality. We also predicted YLL049W as a new member of the dynein-dynactin pathway and provided new supporting experimental evidence. We performed synthetic lethal screens of the parallel mitotic exit network ( MEN) and Cdc14 early anaphase release pathways required for late cell cycle. Synthetic lethal interactions bridged genes in these pathways, and high congruence linked genes within each pathway. Synthetic lethal interactions between MEN and all components of the Sin3/Rpd3 histone deacetylase revealed a novel function for Sin3/Rpd3 in promoting mitotic exit in parallel to MEN. These in silico methods can predict phenotypes and gene functions and are applicable to genomic synthetic lethality screens in yeast and analogous RNA interference screens in metazoans.