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Sci Adv. 2018 May 16;4(5):eaar2740. doi: 10.1126/sciadv.aar2740. eCollection 2018 May.

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

Author information

1
CRCM, CNRS, INSERM, Aix-Marseille Université, Institut Paoli-Calmettes, Equipe Labellisée Ligue, 27 Boulevard Lei Roure, Marseille, France.
2
Telomere and Genome Stability Laboratory, Instituto Gulbenkian de Ciência, Oeiras, Portugal.
3
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA.
4
Institute for Research on Cancer and Aging, Nice, Faculty of Medicine, CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, Nice, France.

Abstract

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.

PMID:
29774234
PMCID:
PMC5955624
DOI:
10.1126/sciadv.aar2740
[Indexed for MEDLINE]
Free PMC Article

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