Format

Send to

Choose Destination
FEMS Yeast Res. 2016 Nov;16(7). pii: fow085. Epub 2016 Sep 27.

Replication stress as a source of telomere recombination during replicative senescence in Saccharomyces cerevisiae.

Author information

1
Centre de Recherche en Cancérologie de Marseille, 'Equipe labellisée Ligue Contre le Cancer', Inserm U1068, Marseille F-13009, France; CNRS, UMR7258, Marseille F-13009; Institut Paoli-Calmettes, Marseille F-13009, France; Aix-Marseille University, UM 105, Marseille F-13284, France marie-noelle.simon@inserm.fr.
2
Centre de Recherche en Cancérologie de Marseille, 'Equipe labellisée Ligue Contre le Cancer', Inserm U1068, Marseille F-13009, France; CNRS, UMR7258, Marseille F-13009; Institut Paoli-Calmettes, Marseille F-13009, France; Aix-Marseille University, UM 105, Marseille F-13284, France.

Abstract

Replicative senescence is triggered by short unprotected telomeres that arise in the absence of telomerase. In addition, telomeres are known as difficult regions to replicate due to their repetitive G-rich sequence prone to secondary structures and tightly bound non-histone proteins. Here we review accumulating evidence that telomerase inactivation in yeast immediately unmasks the problems associated with replication stress at telomeres. Early after telomerase inactivation, yeast cells undergo successive rounds of stochastic DNA damages and become dependent on recombination for viability long before the bulk of telomeres are getting critically short. The switch from telomerase to recombination to repair replication stress-induced damage at telomeres creates telomere instability, which may drive further genomic alterations and prepare the ground for telomerase-independent immortalization observed in yeast survivors and in 15% of human cancer.

KEYWORDS:

recombination; repair; replication stress; replicative senescence; survivors; telomere

PMID:
27683094
DOI:
10.1093/femsyr/fow085
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center