Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing
Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing
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DOI：
10.1093/emboj/17.6.1819
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发表时间：
1998-03-16
期刊：
影响因子：
11.4
通讯作者：
Jackson, SP
中科院分区：
文献类型：
--
作者：
Boulton, SJ;Jackson, SP
在芽殖酵母酿酒酵母中，端粒附近的基因通过端粒位置效应（TPE）的过程受到转录沉默。在这里，我们表明，蛋白Ku，以前参与DNA双链断裂（DSE）修复和端粒长度维持，也是端粒沉默所必需的。此外，使用体内质粒重连接试验，我们证明了SIR2，SIR3和SIR4是先前显示在TPE中起作用的三个基因，对于Ku依赖性DSB修复是必需的。与Ku缺陷型菌株的情况一样，在SIR基因产物不存在的情况下，残余修复通过导致末端缺失的易错DNA修复途径进行，我们已经测试了几个其他的候选基因，它们参与DNA DSB修复、端粒维持和TPE。我们表明TEL1，端粒长度维持所需的基因，对于DNA DSB修复或TPE都不是必需的，然而，RAD 50，MRE11和XRS2在Ku依赖的DNA DSB修复和端粒长度维持中均起作用，尽管它们对TPE没有重大影响。这些数据提供了对DNA DSB修复以及该过程与端粒长度稳态和转录沉默的联系的重要见解。
In the budding yeast, Saccharomyces cerevisiae, genes in close proximity to telomeres are subject to transcriptional silencing through the process of telomere position effect (TPE), Here, we show that the protein Ku, previously implicated in DNA double-strand break (DSE) repair and in telomeric length maintenance, is also essential for telomeric silencing, Furthermore, using an in vivo plasmid rejoining assay, we demonstrate that SIR2, SIR3 and SIR4, three genes shown previously to function in TPE, are essential for Ku-dependent DSB repair, As is the case for Ku-deficient strains, residual repair operating in the absence of the SIR gene products ensues through an error-prone DNA repair pathway that results in terminal deletions, To identify novel components of the Ku-associated DSB repair pathway, we have tested several other candidate genes for their involvement in DNA DSB repair, telomeric maintenance and TPE, We show that TEL1, a gene required for telomeric length maintenance, is not required for either DNA DSB repair or TPE, However, RAD50, MRE11 and XRS2 function both in Ku-dependent DNA DSB repair and in telomeric length maintenance, although they have no major effects on TPE, These data provide important insights into DNA DSB repair and the linkage of this process to telomere length homeostasis and transcriptional silencing.