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

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.

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Author Mennie, Amanda K.
Last Updated November 20, 2019, 16:52 (UTC)
Created November 4, 2019, 17:57 (UTC)
Article Host Type publisher
Article Is Open Access true
Article License Type cc-by
Article Version Type publishedVersion
Citation Report
DOI 10.1038/s42003-019-0546-8
Date Last Updated 2019-11-04T17:56:45.248075
Evidence oa journal (via doaj)
Funder code(s) Ministry of Education, Culture, Sports, Science and Technology (16K15094); Takeda Science Foundation (); Naito Foundation (); National Institutes of Health (GM078253)
Journal Is Open Access true
Open Access Status gold
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