The POT1-TPP1 telomere complex is a telomerase processivity factor
The POT1-TPP1 telomere complex is a telomerase processivity factor
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DOI：
10.1038/nature05454
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发表时间：
2007-02-01
期刊：
影响因子：
64.8
通讯作者：
Lei, Ming
中科院分区：
文献类型：
--
作者：
Wang, Feng;Podell, Elaine R.;Lei, Ming
端粒最初被定义为染色体帽，其防止线性染色体的天然末端发生有害的降解和融合事件。POT 1（端粒保护）蛋白结合人类染色体末端的单链富含G的DNA突出端，并抑制不需要的DNA修复活性。TPP 1是先前鉴定的POT 1的结合伴侣，其已被提出在端粒处形成六蛋白shelterin复合物的一部分。在这里，一个域的人TPP 1的晶体结构揭示了一个寡核苷酸/寡糖结合折叠，在结构上类似于一个纤毛原生动物的端粒末端结合蛋白的β-亚基，这表明TPP 1是人类POT 1蛋白的缺失的β-亚基。端粒DNA末端结合蛋白通常被发现抑制而不是刺激染色体末端复制酶端粒酶的作用。相反，我们发现TPP 1和POT 1与端粒DNA形成复合物，增加了人类端粒酶核心酶的活性和持续合成能力。我们建议，POT 1-TPP 1开关从抑制端粒酶进入端粒，作为一个组成部分的shelterin，作为一个端粒延伸过程中端粒酶的持续合成因子。
Telomeres were originally defined as chromosome caps that prevent the natural ends of linear chromosomes from undergoing deleterious degradation and fusion events. POT1 ( protection of telomeres) protein binds the single-stranded G-rich DNA overhangs at human chromosome ends and suppresses unwanted DNA repair activities. TPP1 is a previously identified binding partner of POT1 that has been proposed to form part of a six-protein shelterin complex at telomeres. Here, the crystal structure of a domain of human TPP1 reveals an oligonucleotide/oligosaccharide-binding fold that is structurally similar to the beta-subunit of the telomere end-binding protein of a ciliated protozoan, suggesting that TPP1 is the missing beta-subunit of human POT1 protein. Telomeric DNA end-binding proteins have generally been found to inhibit rather than stimulate the action of the chromosome end-replicating enzyme, telomerase. In contrast, we find that TPP1 and POT1 form a complex with telomeric DNA that increases the activity and processivity of the human telomerase core enzyme. We propose that POT1 - TPP1 switches from inhibiting telomerase access to the telomere, as a component of shelterin, to serving as a processivity factor for telomerase during telomere extension.