AbstractCommon fragile sites (CFSs) are large chromosomal regions that exhibit breakage on metaphase chromosomes upon replication stress. They become preferentially unstable at the early stage of cancer development and are hotspots for chromosomal rearrangements in cancers. Increasing evidence has highlighted the complexity underlying the instability of CFSs, and a combination of multiple mechanisms is believed to cause CFS fragility. We will review recent advancements in our understanding of the molecular mechanisms underlying the maintenance of CFS stability and the relevance of CFSs to cancer-associated genome instability. We will emphasize the contribution of the structure-prone AT-rich sequences to CFS instability, which is in line with the recent genome-wide study showing that structure-forming repeat sequences are principal sites of replication stress.

中文翻译：

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常见脆弱部位：保护与修复

摘要常见脆弱位点 (CFS) 是大型染色体区域，在复制压力下会在中期染色体上表现出断裂。它们在癌症发展的早期阶段优先变得不稳定，并且是癌症中染色体重排的热点。越来越多的证据凸显了 CFS 不稳定背后的复杂性，多种机制的结合被认为是导致 CFS 脆弱性的原因。我们将回顾对维持 CFS 稳定性的分子机制以及 CFS 与癌症相关基因组不稳定性的相关性的最新进展。我们将强调结构倾向丰富的 AT 序列对 CFS 不稳定的贡献，这与最近的全基因组研究一致，表明结构形成重复序列是复制应激的主要位点。