Institut Curie, CNRS, UMR 144, Sorbonne University, 26 rue d'Ulm, 75005 Paris, France.
DNA Repair (Amst). 2023 Oct;130:103569. doi: 10.1016/j.dnarep.2023.103569. Epub 2023 Sep 7.
Centromeres play a key role in the maintenance of genome stability to prevent carcinogenesis and diseases. They are specialized chromosome loci essential to ensure faithful transmission of genomic information across cell generations by mediating the interaction with spindle microtubules. Nonetheless, while fulfilling these essential roles, their distinct repetitive composition and susceptibility to mechanical stresses during cell division render them susceptible to breakage events. In this review, we delve into the present understanding of the underlying causes of centromere fragility, from the mechanisms governing its DNA replication and repair, to the pathways acting to counteract potential challenges. We propose that the centromere represents a "Trojan horse" exerting vital functions that, at the same time, potentially threatens whole genome stability.
着丝粒在维持基因组稳定性方面起着关键作用,以防止致癌和疾病的发生。它们是专门的染色体位点,对于通过介导与纺锤体微管的相互作用来确保基因组信息在细胞世代之间的忠实传递是必不可少的。尽管发挥着这些重要作用,但它们独特的重复组成和在细胞分裂过程中对机械应力的敏感性,使它们容易发生断裂事件。在这篇综述中,我们深入探讨了目前对着丝粒脆弱性的潜在原因的理解,从控制其 DNA 复制和修复的机制,到作用于抵消潜在挑战的途径。我们提出,着丝粒代表了一个“特洛伊木马”,发挥着重要的功能,同时也可能威胁到整个基因组的稳定性。