Voutsinos Vasileios, Munk Sebastian H N, Oestergaard Vibe H
Department of Biology, University of Copenhagen, 2200 Copenhagen N, Denmark.
Genes (Basel). 2018 Nov 27;9(12):580. doi: 10.3390/genes9120580.
In order to pass on an intact copy of the genome during cell division, complete and faithful DNA replication is crucial. Yet, certain areas of the genome are intrinsically challenging to replicate, which manifests as high local mutation propensity. Such regions include trinucleotide repeat sequences, common chromosomal fragile sites (CFSs), and early replicating fragile sites (ERFSs). Despite their genomic instability CFSs are conserved, suggesting that they have a biological function. To shed light on the potential function of CFSs, this review summarizes the similarities and differences of the regions that challenge DNA replication with main focus on CFSs. Moreover, we review the mechanisms that operate when CFSs fail to complete replication before entry into mitosis. Finally, evolutionary perspectives and potential physiological roles of CFSs are discussed with emphasis on their potential role in neurogenesis.
为了在细胞分裂过程中传递完整的基因组拷贝，完整且忠实的DNA复制至关重要。然而，基因组的某些区域在本质上难以复制，这表现为局部高突变倾向。这些区域包括三核苷酸重复序列、常见染色体脆性位点（CFSs）和早期复制脆性位点（ERFSs）。尽管CFSs具有基因组不稳定性，但它们是保守的，这表明它们具有生物学功能。为了阐明CFSs的潜在功能，本综述总结了挑战DNA复制区域的异同，主要聚焦于CFSs。此外，我们回顾了CFSs在进入有丝分裂之前未能完成复制时所涉及的机制。最后，讨论了CFSs的进化观点和潜在生理作用，重点强调了它们在神经发生中的潜在作用。
