Simon Marie-Noëlle, Churikov Dmitri, Géli Vincent
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
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.
FEMS Yeast Res. 2016 Nov;16(7). doi: 10.1093/femsyr/fow085. Epub 2016 Sep 27.
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.
复制性衰老由端粒酶缺失时出现的短的无保护端粒引发。此外，端粒因其富含鸟嘌呤的重复序列易于形成二级结构且与非组蛋白紧密结合，被认为是难以复制的区域。在此，我们综述了越来越多的证据，表明酵母中端粒酶失活会立即揭示与端粒复制应激相关的问题。端粒酶失活后不久，酵母细胞会经历连续几轮随机的DNA损伤，并在大部分端粒严重缩短之前很久就变得依赖重组来维持生存能力。从端粒酶到重组以修复端粒处复制应激诱导的损伤的转变会产生端粒不稳定，这可能会推动进一步的基因组改变，并为酵母幸存者和15%的人类癌症中观察到的不依赖端粒酶的永生化奠定基础。
