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

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Abstract

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/Rad^3ATR-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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Xichan Hu

Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, United States

Competing interests
The authors declare that no competing interests exist.
Jinqiang Liu

Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, United States

Competing interests
The authors declare that no competing interests exist.
Hyun-IK Jun

Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, United States

Competing interests
The authors declare that no competing interests exist.
Jin-Kwang Kim

Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, United States

Competing interests
The authors declare that no competing interests exist.
Feng Qiao

Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, United States

For correspondence
qiao@uci.edu

Competing interests
The authors declare that no competing interests exist.

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