Telomerase, Ku, and telomeric silencing in Saccharomyces cerevisiae
Telomerase, Ku, and telomeric silencing in Saccharomyces cerevisiae
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DOI：
10.1007/s004120050318
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发表时间：
1998-12-01
期刊：
影响因子：
1.6
通讯作者：
Lundblad, V
中科院分区：
文献类型：
--
作者：
Evans, SK;Sistrunk, ML;Lundblad, V
端粒包含与基因组其余部分的标准核小体结构不同的特化染色体末端结构。端粒的维持和染色体的稳定需要端粒序列的复制和端粒末端的保护，通过蛋白质的结合。我们已经表明，Cdc13 p和异源二聚体Ku是必需的，沿着端粒酶，完整的端粒功能，我们已经提出，Ku和Cdc13 p贡献不同的作用，在结束保护。Ku最近被证明在端粒近端基因的转录抑制中表现出缺陷，称为端粒位置效应（TPE）或端粒沉默。我们在这里调查是否在端粒酶通路中涉及的基因的改变也表现出TPE缺陷，并发现EST1或EST2的缺失或过表达不会显着影响端粒沉默。然而，端粒沉默是解阻遏后，过表达的某些非功能性等位基因的每一个。此外，我们确定端粒酶途径组分的过度产生部分地弥补了hdfl δ细胞中的TPE缺陷。这表明这两种端粒维持途径之间存在遗传串扰，并表明端粒酶途径组分的过量产生可能至少部分地补偿Ku在维持端粒沉默中的损失。
Telomeres comprise a specialized chromosome end structure distinct from the standard nucleosomal architecture of the remainder of the genome. Telomere maintenance and chromosome stability require both replication of telomeric sequences by telomerase and telomeric end protection through binding of proteins. We have shown that Cdc13p and the heterodimer Ku are required, along with telomerase, for full telomere function, and we have proposed that Ku and Cdc13p contribute distinct roles in end protection. Ku has recently been shown to exhibit defects in transcriptional repression of telomere-proximal genes, known as telomere position effect (TPE), or telomeric silencing. We investigate here whether alterations in genes involved in the telomerase pathway also exhibit TPE defects and find that deletion or overexpression of EST1 or EST2 does not significantly affect telomeric silencing. However, telomeric silencing is derepressed upon overexpression of certain nonfunctional alleles of each. In addition, we determined that overproduction of telomerase pathway components partially alleviates the TPE defect in hdfl Delta cells. This indicates that there is genetic crosstalk between these two telomere maintenance pathways, and suggests that overproduction of telomerase pathway components may at least partially compensate for the loss of Ku in maintaining telomeric silencing.