The fission yeast Stn1-Ten1 complex limits telomerase activity via its SUMO-interacting motif and promotes telomeres replication

Matmati, Samah; Vaurs, Mélina; Escandell, José M; Maestroni, Laetitia; Nakamura, Toru M; Ferreira, Miguel G; Géli, Vincent; Coulon, Stéphane

http://hdl.handle.net/10400.7/878

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Abstract(s)

Mammalian CST (CTC1-STN1-TEN1) complex fulfills numerous functions including rescue of the stalled replication forks and termination of telomerase action. In fission yeast lacking the CTC1 ortholog, the Stn1-Ten1 complex restricts telomerase action via its sumoylation-mediated interaction with Tpz1TPP1. We identify a small ubiquitin-like modifier (SUMO)-interacting motif (SIM) in the carboxyl-terminal part of Stn1 and show that this domain is crucial for SUMO and Tpz1-SUMO interactions. Point mutations in the SIM (Stn1-226) lead to telomere elongation, impair Stn1-Ten1 recruitment to telomeres, and enhance telomerase binding, revealing that Stn1 SIM domain contributes to the inhibition of telomerase activity at chromosome ends. Our results suggest that Stn1-Ten1 promotes DNA synthesis at telomeres to limit single-strand DNA accumulation. We further demonstrate that Stn1 functions in the replication of telomeric and subtelomeric regions in a Taz1-independent manner. Genetic analysis reveals that misregulation of origin firing and/or telomerase inhibition circumvents the replication defects of the stn1-226 mutant. Together, our results show that the Stn1-Ten1 complex has a dual function at telomeres by limiting telomerase action and promoting chromosome end replication.

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This deposit is composed by a publication in which the IGC's authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and can only be accessed by two ways: either by requesting a legal copy from the author (the email contact present in this deposit) or by visiting the following link: http://advances.sciencemag.org/content/4/5/eaar2740.full

Keywords

CST Complex telomerase SUMO-interacting Stn1-Ten1 complex chromosome replication DNA replication Taz1 Stn1 protein fission yeast

URI

http://hdl.handle.net/10400.7/878

Citation

S. Matmati, M. Vaurs, J. M. Escandell, L. Maestroni, T. M. Nakamura, M. G. Ferreira, V. Géli, S. Coulon, The fission yeast Stn1-Ten1 complex limits telomerase activity via its SUMOinteracting motif and promotes telomeres replication. Sci. Adv. 4, eaar2740 (2018).