Genome-wide synthetic lethal screens identify an interaction between the nuclear envelope protein, Apq12p, and the kinetochore in Saccharomyces cerevisiae
Genome-wide synthetic lethal screens identify an interaction between the nuclear envelope protein, Apq12p, and the kinetochore in Saccharomyces cerevisiae
复制标题
DOI：
10.1534/genetics.105.045799
复制
发表时间：
2005-10-01
期刊：
影响因子：
3.3
通讯作者：
Measday, V
中科院分区：
文献类型：
--
作者：
Montpetit, B;Thorne, K;Measday, V
基因组稳定性的维持是正常细胞周期进程的基本要求。芽殖酵母酿酒酵母是一个很好的模型来研究染色体的维护，由于其明确的着丝粒和动粒，染色体和相关的蛋白质复合物的区域，分别连接染色体和微管。为了鉴定与染色体稳定性相关的基因，我们使用编码中央和外部动粒蛋白的基因中的一系列新的温度敏感性突变进行了全基因组合成致死筛选。通过使用每个基因的不同突变等位基因进行筛选，我们旨在鉴定揭示影响染色体稳定性的不同途径的遗传相互作用。我们的研究，这是第一个例子的全基因组合成致死筛选与多个等位基因的一个基因，表明功能不同的突变体揭示了不同的细胞过程所需的染色体维护。我们的两个筛选鉴定了APQ12，其编码mRNA的适当核质转运所需的核膜蛋白。我们发现apq12突变体在后期延迟，重新复制其DNA，并在胞质分裂完成之前重新发芽，这表明在控制有丝分裂进程方面存在缺陷。我们的分析揭示了一种新的核质转运和染色体稳定性之间的关系。
The maintenance of genome stability is a fundamental requirement for normal cell cycle progression. The budding yeast Saccharomyces cerevisiae is an excellent model to study chromosome maintenance due to its well-defined centromere and kinetochore, the region of the chromosome and associated protein complex, respectively, that link chromosomes to microtubules. To identify genes that are linked to chromosome stability, we performed genome-wide synthetic lethal screens using a series of novel temperature sensitive mutations in genes encoding a central and outer kinetochore protein. By performing the screens using different Mutant alleles of each gene, we aimed to identify genetic interactions that revealed diverse pathways affecting chromosome stability. Our study, which is the first example of genome-wide synthetic lethal screening with multiple alleles of a single gene, demonstrates that functionally distinct mutants uncover different cellular processes required for chromosome maintenance. Two of our screens identified APQ12, which encodes a nuclear envelope protein that is required for proper nucleocytoplasmic transport of mRNA. We find that apq12 mutants are delayed in anaphase, rereplicate their DNA, and rebud prior to completion of cytokinesis, suggesting a defect in controlling mitotic progression. Our analysis reveals a novel relationship between nucleocytoplasmic transport and chromosome stability.