文章：

癌症生物学中DNA损伤和生存与死亡之间的平衡

DNA damage and the balance between survival and death in cancer biology

原文发布日期：2015-12-18

DOI: 10.1038/nrc.2015.2

类型: Review Article

开放获取: 否

要点：

1. The constant deleterious modification of DNA by reactive molecules, endogenously or exogenously generated, is offset by protective processes that are initiated by the DNA damage response.
2. The interplay of the diverse signalling cascades (DNA damage response) that originate from the interference of DNA lesions with replication and the transcriptome leads to the activation of DNA repair, autophagy, senescence, apoptosis and necroptosis.
3. Aspects of how post-translational modifications of the tumour suppressor p53 determine the switch between these end points are discussed.
4. The crosstalk between autophagy, senescence, apoptosis and regulated necrosis is also discussed, focusing on the importance of thresholds for deciding cell fate.
5. Throughout this Review, emphasis is placed on how DNA damage and DNA repair fit within the complex cellular context.

要点翻译：

1. 内源性或外源性活性分子对DNA持续进行的有害修饰，可通过DNA损伤反应启动的保护性过程得以抵消。
2. DNA病变与复制和转录组的干扰所产生的多种信号级联（DNA损伤反应）相互作用，导致DNA修复、自噬、衰老、凋亡和坏死性凋亡的激活。
3. 本文讨论了肿瘤抑制蛋白p53的翻译后修饰如何决定这些终点之间的转换。
4. 同时还探讨了自噬、衰老、凋亡和调节性坏死之间的相互作用，重点关注决定细胞命运的阈值重要性。
5. 在本综述中，重点强调了DNA损伤和DNA修复如何在复杂的细胞环境中发挥作用。

英文摘要：

DNA is vulnerable to damage resulting from endogenous metabolites, environmental and dietary carcinogens, some anti-inflammatory drugs, and genotoxic cancer therapeutics. Cells respond to DNA damage by activating complex signalling networks that decide cell fate, promoting not only DNA repair and survival but also cell death. The decision between cell survival and death following DNA damage rests on factors that are involved in DNA damage recognition, and DNA repair and damage tolerance, as well as on factors involved in the activation of apoptosis, necrosis, autophagy and senescence. The pathways that dictate cell fate are entwined and have key roles in cancer initiation and progression. Furthermore, they determine the outcome of cancer therapy with genotoxic drugs. Understanding the molecular basis of these pathways is important not only for gaining insight into carcinogenesis, but also in promoting successful cancer therapy. In this Review, we describe key decision-making nodes in the complex interplay between cell survival and death following DNA damage.

摘要翻译： 

DNA易受到内源性代谢产物、环境与饮食致癌物、某些抗炎药物以及基因毒性肿瘤治疗药物的损伤。细胞通过激活复杂的信号网络来应对DNA损伤，这些网络决定细胞命运，不仅促进DNA修复与存活，也促使细胞死亡。DNA损伤后细胞是存活还是死亡，取决于参与DNA损伤识别、修复和耐受的因素，也取决于激活凋亡、坏死、自噬和衰老的相关因子。决定细胞命运的通路相互交织，在癌症的发生与进展中起关键作用，并决定基因毒性药物治疗的效果。阐明这些通路的分子基础，不仅有助于深入理解致癌机制，也对提高癌症治疗成功率至关重要。本综述将描述DNA损伤后细胞存活与死亡复杂相互作用中的关键决策节点。

原文链接：

DNA damage and the balance between survival and death in cancer biology