文章：

复制应激和癌症

Replication stress and cancer

原文发布日期：2015-04-24

DOI: 10.1038/nrc3916

类型: Review Article

开放获取: 否

要点：

1. Replication is a highly regulated process that guarantees the faithful duplication of the genome once per cell cycle, and any condition that compromises it is referred to as replication stress.
2. Replication stress is a major cause of genome instability and is linked to pre-tumour and tumour cells. Several oncogenes cause alterations of replication timing and progression, leading to replication stress.
3. The DNA-damage checkpoint responds to replication stress to guarantee genome stability by protecting stalled forks and promoting replication completion through the activation of dormant replication origins.
4. DNA repair pathways such as homologous recombination restore replication upon DNA breaks that occur at stalled forks.
5. Failures in the cellular response to replication stress, such as those caused by dysfunctions of the DNA-damage checkpoint, replication fork restart or DNA repair, are tumorigenic, as seen in mouse models and human syndromes.
6. Replication stress is not a common feature of normal cells; therefore, it opens up new possibilities for cancer diagnostics and treatment.

要点翻译：

1. 复制是一个高度调控的过程，确保每个细胞周期中基因组的精确复制，任何破坏这一过程的情况都被称为复制压力。
2. 复制压力是基因组不稳定的主要原因，并与前肿瘤细胞和肿瘤细胞相关。若干癌基因会引起复制时序和进程的改变，从而导致复制压力。
3. DNA损伤检查点通过保护停滞的复制叉并通过激活休眠复制起点促进复制完成，来应对复制压力，从而确保基因组的稳定性。
4. 同源重组等DNA修复途径可在停滞复制叉处发生DNA断裂时恢复复制过程。
5. 细胞对复制压力的应答失败（例如由DNA损伤检查点功能异常、复制叉重启失败或DNA修复缺陷所引起）具有致瘤性，这在小鼠模型和人类综合征中已得到证实。
6. 复制压力并非正常细胞的常见特征，因此这为癌症诊断和治疗开辟了新的可能性。

英文摘要：

Genome instability is a hallmark of cancer, and DNA replication is the most vulnerable cellular process that can lead to it. Any condition leading to high levels of DNA damage will result in replication stress, which is a source of genome instability and a feature of pre-cancerous and cancerous cells. Therefore, understanding the molecular basis of replication stress is crucial to the understanding of tumorigenesis. Although a negative aspect of replication stress is its prominent role in tumorigenesis, a positive aspect is that it provides a potential target for cancer therapy. In this Review, we discuss the link between persistent replication stress and tumorigenesis, with the goal of shedding light on the mechanisms underlying the initiation of an oncogenic process, which should open up new possibilities for cancer diagnostics and treatment.

摘要翻译： 

基因组不稳定性是癌症的标志之一，而DNA复制是最易导致这种不稳定性的细胞过程。任何导致高水平DNA损伤的情况都会引发复制压力，这是基因组不稳定性的来源，也是癌前细胞和癌细胞的特征。因此，理解复制压力的分子基础对于理解肿瘤发生至关重要。尽管复制压力的负面方面在于其在肿瘤发生中的突出作用，但其积极方面在于它为癌症治疗提供了潜在的靶点。在本综述中，我们讨论了持续性复制压力与肿瘤发生之间的联系，旨在阐明致癌过程启动的机制，这应为癌症诊断和治疗开辟新的可能性。

原文链接：

Replication stress and cancer