The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation
The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation
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DOI：
10.1091/mbc.e10-06-0549
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发表时间：
2011-05-15
影响因子：
3.3
通讯作者：
Donaldson, Anne D.
中科院分区：
文献类型：
--
作者：
Lian, Hui-Yong;Robertson, E. Douglas;Donaldson, Anne D.
酿酒酵母中的DNA复制根据时间程序进行。我们已经研究了端粒结合Ku复合物在指定端粒近端序列的后期复制中的作用。全基因组分析表明，从端粒延伸到80 kb的区域在yku 70突变体中异常早期复制。我们发现，Ku并没有出现调节复制时间直接结合复制起点，也不是它的影响端粒复制时间介导的组蛋白尾部乙酰化。我们表明，Ku，而不是通过其对端粒长度的影响调节复制时间，因为删除端粒酶调节Pif 1在很大程度上逆转了短端粒缺陷的yku 70突变体，同时挽救其复制时间缺陷。与这一结论相一致，删除基因组完整性组件Elg 1部分挽救了yku 70端粒的长度和复制时间。端粒长度介导的复制时间控制需要TG（1-3）重复计数组件Rif 1，因为rif 1突变体复制端粒区域早，尽管有延长的TG（1-3）tracts。总的来说，我们的研究结果表明，Ku对端粒复制时间的影响来自其对TG（1-3）重复长度的影响，并支持Rif 1测量端粒重复长度以确保端粒复制时间正确编程的模型。
DNA replication in Saccharomyces cerevisiae proceeds according to a temporal program. We have investigated the role of the telomere-binding Ku complex in specifying late replication of telomere-proximal sequences. Genome-wide analysis shows that regions extending up to 80 kb from telomeres replicate abnormally early in a yku70 mutant. We find that Ku does not appear to regulate replication time by binding replication origins directly, nor is its effect on telomere replication timing mediated by histone tail acetylation. We show that Ku instead regulates replication timing through its effect on telomere length, because deletion of the telomerase regulator Pif1 largely reverses the short telomere defect of a yku70 mutant and simultaneously rescues its replication timing defect. Consistent with this conclusion, deleting the genome integrity component Elg1 partially rescued both length and replication timing of yku70 telomeres. Telomere length-mediated control of replication timing requires the TG(1-3) repeat-counting component Rif1, because a rif1 mutant replicates telomeric regions early, despite having extended TG(1-3) tracts. Overall, our results suggest that the effect of Ku on telomere replication timing results from its impact on TG(1-3) repeat length and support a model in which Rif1 measures telomere repeat length to ensure that telomere replication timing is correctly programmed.