Wang Feng, Lei Ming
Department of Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI, USA.
Methods Mol Biol. 2011;735:173-87. doi: 10.1007/978-1-61779-092-8_17.
Telomeres, the specialized DNA-protein complexes found at the termini of all linear eukaryotic -chromosomes, protect chromosomes from degradation and end-to-end fusion. The protection of telomeres 1 (POT1) protein binds the single-stranded overhang at the ends of chromosomes in diverse eukaryotes. It is essential for chromosome end-protection and involved in telomere length regulation. TPP1 is a previously identified binding partner of POT1 that has been proposed to form part of a -six-protein shelterin complex at telomeres. Through structural and biochemical studies, we have -demonstrated that human TPP1 is the missing human homolog of the β subunit of protozoan telomere end-binding-protein-complex (TEBPα-TEBPβ). Therefore, capping of telomeres by a TEBPα-TEBPβ/POT1-TPP1 dimer is more evolutionarily conserved than that had been expected. In addition, we also discovered that the human POT1-TPP1 complex is a processivity factor for telomerase.
端粒是存在于所有线性真核染色体末端的特殊DNA-蛋白质复合物，可保护染色体免于降解和端对端融合。端粒保护蛋白1（POT1）在多种真核生物中与染色体末端的单链悬突结合。它对染色体末端保护至关重要，并参与端粒长度调节。TPP1是先前鉴定出的POT1结合伴侣，有人提出它是端粒上六蛋白保护素复合物的一部分。通过结构和生化研究，我们证明人类TPP1是原生动物端粒末端结合蛋白复合物（TEBPα-TEBPβ）β亚基缺失的人类同源物。因此，由TEBPα-TEBPβ/POT1-TPP1二聚体对端粒进行加帽在进化上比预期更为保守。此外，我们还发现人类POT1-TPP1复合物是端粒酶的一个持续性因子。
