Telomere protection by mammalian Pot1 requires interaction with Tpp1

Telomere protection by mammalian Pot1 requires interaction with Tpp1
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DOI:
10.1038/nsmb1270
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发表时间:
2007-08-01
影响因子:
16.8
通讯作者:
Hammer, Gary D.
Hammer, Gary D.
中科院分区:
生物学1区
文献类型:
--
作者:
Hockemeyer, Dirk;Palm, Wilhelm;Hammer, Gary D.

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哺乳动物端粒上的庇护蛋白复合体含有单链 DNA 结合蛋白 Pot1,可调节端粒长度并保护染色体末端。 Pot1 结合 Tpp1,Tpp1 是连接 Pot1 与双链体端粒 DNA 结合蛋白 Trf1 和 Trf2 的庇护蛋白成分。端粒长度的控制需要Pot1结合Tpp1以及单链端粒DNA,但Pot1的保护功能是否依赖于Tpp1尚不清楚。或者,Pot1 的功能可能与芽殖酵母和裂殖酵母的 Pot1 样蛋白类似,后者与双链端粒 DNA 没有已知的 Tpp1 样连接。使用 Tpp1 水平降低的突变小鼠细胞,针对小鼠 Tpp1 和 Pot1 的 RNA 干扰,以及小鼠 Pot1 敲除细胞与人类和小鼠 Pot1 变体的互补,我们在此表明​​ Tpp1 对于哺乳动物 Pot1 蛋白的保护功能是必需的。
The shelterin complex at mammalian telomeres contains the single-stranded DNA-binding protein Pot1, which regulates telomere length and protects chromosome ends. Pot1 binds Tpp1, the shelterin component that connects Pot1 to the duplex telomeric DNA-binding proteins Trf1 and Trf2. Control of telomere length requires that Pot1 binds Tpp1 as well as the single-stranded telomeric DNA, but it is not known whether the protective function of Pot1 depends on Tpp1. Alternatively, Pot1 might function similarly to the Pot1-like proteins of budding and fission yeast, which have no known Tpp1-like connection to the duplex telomeric DNA. Using mutant mouse cells with diminished Tpp1 levels, RNA interference directed to mouse Tpp1 and Pot1, and complementation of mouse Pot1 knockout cells with human and mouse Pot1 variants, we show here that Tpp1 is required for the protective function of mammalian Pot1 proteins.