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Tpz1TPP1 prevents telomerase activation and protects telomeres by modulating the Stn1-Ten1 complex in fission yeast

journal contribution
posted on 2022-11-29, 21:50 authored by Amanda K Mennie, Bettina MoserBettina Moser, Alice Hoyle, Ross S Low, Katsunori Tanaka, Toru NakamuraToru Nakamura
In both mammalian and fission yeast cells, conserved shelterin and CST (CTC1-STN1-TEN1) complexes play critical roles in protection of telomeres and regulation of telomerase, an enzyme required to overcome the end replication problem. However, molecular details that govern proper coordination among shelterin, CST, and telomerase have not yet been fully understood. Here, we establish a conserved SWSSS motif, located adjacent to the Lys242 SUMOylation site in the fission yeast shelterin subunit Tpz1, as a new functional regulatory element for telomere protection and telomere length homeostasis. The SWSSS motif works redundantly with Lys242 SUMOylation to promote binding of Stn1-Ten1 at telomere and sub-telomere regions to protect against single-strand annealing (SSA)-dependent telomere fusions, and to prevent telomerase accumulation at telomeres. In addition, we provide evidence that the SWSSS motif defines an unanticipated role of Tpz1 in limiting telomerase activation at telomeres to prevent uncontrolled telomere elongation.

Funding

Roles of Checkpoint and DNA Repair Proteins in Fission Yeast Telomere Maintenance | Funder: National Institutes of Health (National Institute of General Medical Sciences) | Grant ID: R01GM078253

History

Citation

Mennie, A. K., Moser, B. A., Hoyle, A., Low, R. S., Tanaka, K.Nakamura, T. M. (2019). Tpz1TPP1 prevents telomerase activation and protects telomeres by modulating the Stn1-Ten1 complex in fission yeast. Communications Biology, 2(1), 297-. https://doi.org/10.1038/s42003-019-0546-8

Publisher

Springer Nature

Language

en

issn

2399-3642