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首页> 外文期刊>Molecular and Cellular Biology >Rescue of an hTERT Mutant Defective in Telomere Elongation by Fusion with hPot1
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Rescue of an hTERT Mutant Defective in Telomere Elongation by Fusion with hPot1

机译：通过与hPot1融合挽救端粒延长中的hTERT突变体。

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The protein hPot1 shares homology with telomere-binding proteins in lower eukaryotes and associates with single-stranded telomeric DNA in vitro as well as colocalizing with telomere-binding proteins in vivo. We now show that hPot1 is coimmunoprecipitated with telomeric DNA and that stable expression of this protein in telomerase-positive cells results in telomere elongation, supporting the idea that hPot1 is a bona fide mammalian telomere-binding protein. We previously found that mutations in the N-terminal DAT domain of the hTERT catalytic subunit of telomerase rendered the enzyme catalytically active but unable to elongate telomeres in vivo. This phenotype could be partially rescued by fusion with the double-stranded telomeric protein hTRF2. Given that hPot1 binds to single-stranded DNA in vitro (at the same site that hTERT binds to in vivo), we addressed whether fusion of hPot1 can rescue the DAT mutations more efficiently than that of hTRF2. We now report that a DAT mutant of hTERT is indeed efficiently rescued upon fusion to hPot1. However, this rescue depended on the ability of hPot1 to localize to telomeres rather than binding to DNA per se. These data support a model whereby the DAT domain of hTERT is implicated in telomere-telomerase associations.
机译：hPot1蛋白与低等真核生物中的端粒结合蛋白具有同源性，并在体外与单链端粒DNA结合，并在体内与端粒结合蛋白共定位。现在，我们显示hPot1与端粒DNA共免疫沉淀，并且该蛋白在端粒酶阳性细胞中的稳定表达导致端粒延长，从而支持hPot1是真正的哺乳动物端粒结合蛋白。我们先前发现端粒酶hTERT催化亚基的N端DAT结构域中的突变使该酶具有催化活性，但无法在体内延长端粒。通过与双链端粒蛋白hTRF2融合可以部分挽救该表型。鉴于hPot1在体外与单链DNA结合（在hTERT与体内结合的相同位点），我们研究了hPot1的融合是否比hTRF2能够更有效地挽救DAT突变。我们现在报告，hTERT的DAT突变体在与hPot1融合后确实可以有效拯救。但是，这种拯救取决于hPot1定位于端粒的能力，而不是与DNA本身结合的能力。这些数据支持了一种模型，其中hTERT的DAT结构域与端粒-端粒酶相关。

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