Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes.
Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes.
复制标题
具有端粒复制缺陷的酿酒酵母衰老突变体鉴定出另外三个 EST 基因。
DOI：
10.1093/genetics/144.4.1399
复制
发表时间：
1996
期刊：
影响因子：
3.3
通讯作者：
Lundblad,V
中科院分区：
文献类型：
--
作者：
Lendvay,TS;Morris,DK;Sah,J;Balasubramanian,B;Lundblad,V
端粒复制的主要决定因素是端粒酶，负责延长端粒的富含G的链。在酿酒酵母中已鉴定的这种酶的唯一组分是编码端粒酶RNA亚基的TLC1基因。然而，EST1基因缺陷的酵母菌株表现出与缺失TLC1的菌株相同的表型（端粒逐渐变短和衰老表型），这表明EST1编码端粒酶的一种成分或端粒酶功能所必需的其他因子。我们设计了一个多层次的筛选，分离出22个突变株，它们表现出与est1和tlc1突变株相同的表型。这些突变定位于四个互补组：先前鉴定的EST1基因和另外三个基因，称为EST2、EST3和EST4。EST2基因的克隆表明，它编码一个大的，非常基本的新蛋白质，没有提供功能线索的基序。上位性分析表明，四个EST基因的功能在相同的途径端粒复制所定义的TLC1基因，这表明EST基因编码端粒酶的成分或积极调节端粒酶活性的因素。
The primary determinant for telomere replication is the enzyme telomerase, responsible for elongating the G-rich strand of the telomere. The only component of this enzyme that has been identified inSaccharomyces cermzsiaeis theTLC1gene, encoding the telomerase RNA subunit. However, a yeast strain defective for theEST1gene exhibits the same phenotypes (progressively shorter telomeres and a senescence phenotype) as a strain deleted forTLC1, suggesting thatEST1encodes either a component of telomerase or some other factor essential for telomerase function. We designed a multitiered screen that led to the isolation of22mutants that display the same phenotypes asest1andtlc1mutant strains. These mutations mapped to four complementation groups: the previously identifiedEST1gene and three additional genes, calledEST2, EST3andEST4. Cloning of theEST2gene demonstrated that it encodes a large, extremely basic novel protein with no motifs that provide clues as to function. Epistasis analysis indicated that the fourESTgenes function in the same pathway for telomere replication as defined by theTLC1gene, suggesting that theESTgenes encode either components of telomerase or factors that positively regulate telomerase activity.