Department of Cell and Molecular Biology, Karolinska Institutet , Stockholm, Sweden.
Front Genet. 2015 Feb 27;6:63. doi: 10.3389/fgene.2015.00063. eCollection 2015.
The DNA damage response (DDR) has two main goals, to repair the damaged DNA and to communicate the presence of damaged DNA. This communication allows the adaptation of cellular behavior to minimize the risk associated with DNA damage. In particular, cell cycle progression must be adapted after a DNA-damaging insult, and cells either pause or terminally exit the cell cycle during a DDR. As cells can accumulate mutations after a DDR due to error-prone DNA repair, terminal cell cycle exit may prevent malignant transformation. The tumor suppressor p53 plays a key role in promoting terminal cell cycle exit. Interestingly, p53 has been implicated in communication of a stress response to surrounding cells, known as the bystander response. Recently, surrounding cells have also been shown to affect the damaged cell, suggesting the presence of intercellular feedback loops. How such feedback may affect terminal cell cycle exit remains unclear, but its presence calls for caution in evaluating cellular outcome without controlling the cellular surrounding. In addition, such feedback may contribute to how the cellular environment affects malignant transformation after DNA damage.
DNA 损伤反应（DDR）有两个主要目标，一是修复受损的 DNA，二是传递受损 DNA 的存在。这种通讯使细胞行为能够适应，从而最大限度地降低与 DNA 损伤相关的风险。特别是，在 DNA 损伤后，细胞周期进程必须适应，细胞在 DDR 期间要么暂停，要么终止细胞周期。由于细胞在 DDR 后可能会因易错 DNA 修复而积累突变，因此终末细胞周期退出可能会阻止恶性转化。肿瘤抑制因子 p53 在促进终末细胞周期退出中起着关键作用。有趣的是，p53 已被牵涉到向周围细胞传递应激反应，即旁观者反应。最近，还表明周围细胞会影响受损细胞，这表明存在细胞间反馈回路。这种反馈如何影响终末细胞周期退出尚不清楚，但它的存在提醒人们，在不控制细胞周围环境的情况下评估细胞结果时要谨慎。此外，这种反馈可能有助于解释细胞环境如何在 DNA 损伤后影响恶性转化。
