A proto-telomere is elongated by telomerase in a shelterin-dependent manner in quiescent fission yeast cells

Author:

Vaurs Mélina1,Audry Julien2,Runge Kurt W23ORCID,Géli Vincent1ORCID,Coulon Stéphane1ORCID

Affiliation:

1. CNRS, INSERM, Aix Marseille Univ, Institut Paoli-Calmettes, CRCM, Equipe labellisée par la Ligue Nationale contre le Cancer , Marseille , F-13009 , France

2. Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation , Cleveland , OH , USA

3. Department of Genetics and Genome Sciences, Case Western Reserve University , Cleveland , OH , USA

Abstract

Abstract Telomere elongation is coupled with genome replication, raising the question of the repair of short telomeres in post-mitotic cells. We investigated the fate of a telomere-repeat capped end that mimics a single short telomere in quiescent fission yeast cells. We show that telomerase is able to elongate this single short telomere during quiescence despite the binding of Ku to the proto-telomere. While Taz1 and Rap1 repress telomerase in vegetative cells, both shelterin proteins are required for efficient telomere extension in quiescent cells, underscoring a distinct mode of telomerase control. We further show that Rad3ATR and Tel1ATM are redundantly required for telomere elongation in quiescence through the phosphorylation of Ccq1 and that Rif1 and its associated-PP1 phosphatases negatively regulate telomerase activity by opposing Ccq1 phosphorylation. The distinct mode of telomerase regulation in quiescent fission yeast cells may be relevant to that in human stem and progenitor cells.

Funder

National Science Foundation

National Institutes of Health

Ligue Nationale Contre le Cancer

Bourse du Ministère de l’Enseignement Supérieur, et de la Recherche

Agence Nationale de la Recherche

Publisher

Oxford University Press (OUP)

Subject

Genetics

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