Human Telomere POT1-TPP1 Complex and Its Role in Telomerase Activity Regulation

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.