Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Int J Mol Sci. 2019 Mar 1;20(5):1073. doi: 10.3390/ijms20051073.
DNA is an entity shielded by mechanisms that maintain genomic stability and are essential for living cells; however, DNA is constantly subject to assaults from the environment throughout the cellular life span, making the genome susceptible to mutation and irreparable damage. Cells are prepared to mend such events through cell death as an extrema ratio to solve those threats from a multicellular perspective. However, in cells under various stress conditions, checkpoint mechanisms are activated to allow cells to have enough time to repair the damaged DNA. In yeast, entry into the cell cycle when damage is not completely repaired represents an adaptive mechanism to cope with stressful conditions. In multicellular organisms, entry into cell cycle with damaged DNA is strictly forbidden. However, in cancer development, individual cells undergo checkpoint adaptation, in which most cells die, but some survive acquiring advantageous mutations and selfishly evolve a conflictual behavior. In this review, we focus on how, in cancer development, cells rely on checkpoint adaptation to escape DNA stress and ultimately to cell death.
DNA 是一种受保护的实体，其机制可维持基因组稳定性，是活细胞所必需的；然而，在整个细胞生命周期中，DNA 不断受到环境的攻击，使基因组易发生突变和不可修复的损伤。细胞准备通过细胞死亡作为解决多细胞层面这些威胁的极端手段来修复这些事件。然而，在各种应激条件下的细胞中，检查点机制被激活，以使细胞有足够的时间来修复受损的 DNA。在酵母中，当损伤未完全修复时进入细胞周期代表了一种应对应激条件的适应机制。在多细胞生物中，严格禁止带有受损 DNA 的细胞进入细胞周期。然而，在癌症发展过程中，个别细胞会发生检查点适应，大多数细胞死亡，但有些细胞存活下来并获得有利的突变，自私地进化出一种冲突的行为。在这篇综述中，我们重点关注在癌症发展过程中，细胞如何依赖检查点适应来逃避 DNA 应激并最终逃避细胞死亡。
