Irony-Tur Sinai Michal, Kerem Batsheva
Department of Genetics, The Life Sciences Institute, The Hebrew University, Jerusalem, 91904, Israel.
Department of Genetics, The Life Sciences Institute, The Hebrew University, Jerusalem, 91904, Israel.
Mutat Res. 2018 Mar;808:56-61. doi: 10.1016/j.mrfmmm.2017.10.002. Epub 2017 Oct 18.
DNA replication stress is one of the early drivers enabling the ongoing acquisition of genetic changes arising during tumorigenesis. As such, it is a feature of most pre-malignant and malignant cells. In this review article, we focus on the early events initiating DNA replication stress and the preferential sensitivity of common fragile sites (CFSs) to this stress. CFSs are specific genomic regions within the normal chromosomal structure, which appear as gaps and breaks in the metaphase chromosomes of cells grown under mild replication stress conditions. The main characteristics predisposing CFSs to instability include late replication timing, delayed replication completion, failure to activate additional origins, origin paucity along large genomic regions, collision between replication and transcription complexes along large genes, and the presence of AT-dinucleotide rich sequences. The contribution of these features to instability at CFSs during early cancer development is discussed.
DNA复制应激是肿瘤发生过程中促使持续获得遗传变化的早期驱动因素之一。因此，它是大多数癌前和恶性细胞的一个特征。在这篇综述文章中，我们聚焦于引发DNA复制应激的早期事件以及常见脆性位点（CFSs）对这种应激的优先敏感性。CFSs是正常染色体结构内的特定基因组区域，在轻度复制应激条件下生长的细胞的中期染色体中表现为间隙和断裂。使CFSs易于出现不稳定性的主要特征包括复制时间晚、复制完成延迟、未能激活额外的复制起点、沿大基因组区域的复制起点稀少、沿大基因的复制和转录复合体之间的碰撞以及富含AT二核苷酸序列的存在。本文讨论了这些特征在癌症早期发展过程中对CFSs不稳定性的影响。
