Sorbonne Université, PSL Research University, CNRS, UMR8226, Institut de Biologie Physico-Chimique, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, 75005, Paris, France.
Sorbonne Université, CNRS, UMR7238, Institut de Biologie Paris-Seine, Laboratory of Computational and Quantitative Biology, 75005, Paris, France.
Curr Genet. 2019 Jun;65(3):711-716. doi: 10.1007/s00294-019-00933-7. Epub 2019 Jan 12.
Cell proliferation is tightly regulated to avoid propagating DNA damage and mutations, which can lead to pathologies such as cancer. To ensure genome integrity, cells activate the DNA damage checkpoint in response to genotoxic lesions to block cell cycle progression. This surveillance mechanism provides time to repair the damage before resuming cell cycle with an intact genome. When the damage is not repaired, cells can, in some conditions, override the cell cycle arrest and proceed with proliferation, a phenomenon known as adaptation to DNA damage. A subpopulation of adapted cells might eventually survive, but only at the cost of extensive genome instability. How and in which context adaptation operates the trade-off between survival and genome stability is a fascinating question. After a brief review of the current knowledge on adaptation to DNA damage in budding yeast, we will discuss a new role of adaptation in the context of telomerase-negative cells and replicative senescence. We highlight the idea that, in all settings studied so far, survival through adaptation is a double-edged sword as it comes with increased genomic instability.
细胞增殖受到严格调控，以避免增殖 DNA 损伤和突变，这些损伤和突变可导致癌症等疾病。为了确保基因组完整性，细胞在受到遗传毒性损伤时会激活 DNA 损伤检查点，以阻止细胞周期进程。这种监控机制为在基因组完整的情况下恢复细胞周期提供了修复损伤的时间。当损伤未被修复时，在某些条件下，细胞可以绕过细胞周期停滞并继续增殖，这种现象称为对 DNA 损伤的适应。适应的细胞亚群最终可能会存活下来，但这是以广泛的基因组不稳定性为代价的。在生存和基因组稳定性之间进行权衡的适应是如何运作的，以及在何种情况下运作，这是一个引人入胜的问题。在简要回顾了芽殖酵母中 DNA 损伤适应的现有知识之后，我们将讨论适应在端粒酶阴性细胞和复制性衰老中的新作用。我们强调了这样一种观点，即在迄今为止研究的所有情况下，通过适应获得的生存都是一把双刃剑，因为它伴随着基因组不稳定性的增加。
