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The fission yeast Stn1-Ten1 complex limits telomerase activity via its SUMO-interacting motif and promotes telomeres replication
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| supplementary materials | 557.45 KB | Adobe PDF |
Orientador(es)
Resumo(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.
Descrição
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
Palavras-chave
CST Complex telomerase SUMO-interacting Stn1-Ten1 complex chromosome replication DNA replication Taz1 Stn1 protein fission yeast
Contexto Educativo
Citação
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).
Editora
American Association for the Advancement of Science