Multi-step coordination of telomerase recruitment in fission yeast through two coupled telomere-telomerase interfaces.

Tightly controlled recruitment of telomerase, a low-abundance enzyme, to telomeres is essential for regulated telomere synthesis. Recent studies in human cells revealed that a patch of amino acids in the shelterin component TPP1, called the TEL-patch, is essential for recruiting telomerase to telomeres. However, how TEL-patch-telomerase interaction integrates into the overall orchestration of telomerase regulation at telomeres is unclear. In fission yeast, Tel1(ATM)/Rad3(ATR)-mediated phosphorylation of shelterin component Ccq1 during late S phase is involved in telomerase recruitment through promoting the binding of Ccq1 to a telomerase accessory protein Est1. Here, we identify the TEL-patch in Tpz1(TPP1), mutations of which lead to decreased telomeric association of telomerase, similar to the phosphorylation-defective Ccq1. Furthermore, we find that telomerase action at telomeres requires formation and resolution of an intermediate state, in which the cell cycle-dependent Ccq1-Est1 interaction is coupled to the TEL-patch-Trt1 interaction, to achieve temporally regulated telomerase elongation of telomeres.

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