New yeast genes important for chromosome integrity and segregation identified by dosage effects on genome stability
New yeast genes important for chromosome integrity and segregation identified by dosage effects on genome stability
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DOI：
10.1093/nar/27.15.3001
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发表时间：
1999-08-01
影响因子：
14.9
通讯作者：
Brinkley, BR
中科院分区：
文献类型：
--
作者：
Ouspenski, II;Elledge, SJ;Brinkley, BR
由基因过表达产生的表型可能为基因功能提供重要线索。在这里，我们已经进行了一个搜索的基因，影响染色体稳定性时，过表达的芽殖酵母酿酒酵母，我们已经获得了克隆涵盖30个不同的基因，这些基因中的二十四个已被先前的特点。它们中的大多数参与染色质动力学、细胞周期控制、DNA复制或有丝分裂染色体分离。通过对CST基因的不稳定性、与检查点突变的相互作用以及对染色体复制或分离抑制剂的敏感性分析，我们认为CST基因4的过表达可以特异性地干扰有丝分裂染色体的分离，而CST基因6影响DNA代谢的某些方面，其他CST基因具有复杂的多效性表型。我们已经创建了在该筛选中获得的五个基因的缺失，CST9，CST13，NAT1，SBA1和FUN30，这些基因中没有一个是生存力所必需的，并且NAT1和SBA1的缺失引起染色体不稳定性，这是先前与这些基因无关的表型。这项工作表明，剂量效应的分析与染色体传递保真度的突变分析是互补的，因为它允许鉴定在突变筛选中未检测到的染色体稳定性基因。
Phenotypes produced by gene overexpression may provide important clues to gene function. Here, we have performed a search for genes that affect chromosome stability when overexpressed in the budding yeast Saccharomyces cerevisiae, We have obtained clones encompassing 30 different genes, Twenty-four of these genes have been previously characterized. Most of them are involved in chromatin dynamics, cell cycle control, DNA replication or mitotic chromosome segregation. Six novel genes obtained in this screen were named CST (chromosome stability), Based on the pattern of genomic instability, interaction with checkpoint mutations and sensitivity to chromosome replication or segregation inhibitors, we conclude that overexpression of CST4 specifically interferes with mitotic chromosome segregation, and CST6 affects some aspect of DNA metabolism, The other CST genes had complex pleiotropic phenotypes. We have created deletions of five genes obtained in this screen, CST9, CST13, NAT1, SBA1 and FUN30, None of these genes is essential for viability, and deletions of NAT1 and SBA1 cause chromosome instability, a phenotype not previously associated with these genes, This work shows that analysis of dosage effects is complementary to mutational analysis of chromosome transmission fidelity, as it allows the identification of chromosome stability genes that have not been detected in mutational screens.