Protection of telomeres by a conserved Stn1-Ten1 complex
Protection of telomeres by a conserved Stn1-Ten1 complex
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DOI：
10.1073/pnas.0705497104
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发表时间：
2007-08-28
影响因子：
11.1
通讯作者：
Russell, Paul
中科院分区：
文献类型：
--
作者：
Martin, Victoria;Du, Li-Lin;Russell, Paul
端粒是保护染色体末端的特殊染色质结构。端粒蛋白中的关键是那些与端粒单链DNA(SsDNA)突出部分结合的蛋白质。这些蛋白质被认为在真核生物中是不同的。三个相互作用的蛋白质(CDC13，Stn1和Ten1)与发芽酵母中的端粒悬垂相关，一个被称为POT1(端粒保护-1)的蛋白质在分裂酵母中执行这一功能，而由POT1和TPP1组成的两个亚单位复合体与人类的端粒单链DNA相关。CDC13和POT1具有相关的寡核苷酸/寡糖结合折叠(OB-Fold)结构域，与端粒单链DNA悬垂结合。在这里，我们发现裂殖酵母具有Stn1和Ten1样蛋白，这些蛋白对于染色体末端保护是必不可少的。Stn1同源基因存在于所有具有POT1的物种中，而Ten1类蛋白则存在于所有真菌中。裂解酵母Stn1和Ten1定位于端粒，其定位方式与单链DNA悬垂的长度相关，这表明它们与端粒单链DNA特异性地结合。在芽生酵母中，CDc13、Stn1和Ten1都相互作用，而分裂酵母Stn1和Ten1彼此关联，但不与POT1关联。我们的发现表明，在分裂酵母中，染色体末端保护需要两个独立的蛋白质复合体。结构谱研究在Stn1和Ten1同源基因中检测到OB-折叠结构域，表明具有OB-折叠结构域的多个蛋白质对端粒的保护在真核进化中是保守的。
Telomeres are specialized chromatin structures that protect chromosome ends. Critical among telomere proteins are those that bind the telomeric single-strand DNA (ssDNA) overhangs. These proteins are thought to differ among eukaryotes. Three interacting proteins (Cdc13, Stn1, and Ten1) associate with the telomeric overhang in budding yeast, a single protein known as Pot1 (protection of telomeres-1) performs this function in fission yeast, and a two-subunit complex consisting of POT1 and TPP1 associates with telomeric ssDNA in humans. Cdc13 and Pot1 have related oligonucleotide/oligosaccharide-binding fold (OB-fold) domains that bind the telomeric ssDNA overhang. Here we show that Schizosaccharomyces pombe has Stn1- and Ten1-like proteins that are essential for chromosome end protection. Stn1 orthologs exist in all species that have Pot1, whereas Ten1-like proteins can be found in all fungi. Fission yeast Stn1 and Ten1 localize at telomeres in a manner that correlates with the length of the ssDNA overhang, suggesting that they specifically associate with the telomeric ssDNA. Unlike in budding yeast, in which Cdc13, Stn1, and Ten1 all interact, fission yeast Stn1 and Ten1 associate with each other, but not with Pot1. Our findings suggest that two separate protein complexes are required for chromosome end protection in fission yeast. Structural profiling studies detect OB-fold domains in Stn1 and Ten1 orthologs, indicating that protection of telomeres by multiple proteins with OB-fold domains is conserved in eukaryotic evolution.