Replication stress as a source of telomere recombination during replicative senescence in Saccharomyces cerevisiae.
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.
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.
Marie-Noëlle
MN
Simon
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.
Dmitri
D
Churikov
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.
Vincent
V
Géli
D016922:Cellular Senescence; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics* / Q000378:metabolism*; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*
D004271:DNA, Fungal; D019098:Telomerase
recombination; repair; replication stress; replicative senescence; survivors; telomere