Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, UK.
Biotech Research and Innovation Centre (BRIC), Health and Medical Faculty, University of Copenhagen, Copenhagen, Denmark.
Adv Exp Med Biol. 2017;1042:311-333. doi: 10.1007/978-981-10-6955-0_15.
Inheritance of the DNA sequence and its proper organization into chromatin is fundamental for genome stability and function. Therefore, how specific chromatin structures are restored on newly synthesized DNA and transmitted through cell division remains a central question to understand cell fate choices and self-renewal. Propagation of genetic information and chromatin-based information in cycling cells entails genome-wide disruption and restoration of chromatin, coupled with faithful replication of DNA. In this chapter, we describe how cells duplicate the genome while maintaining its proper organization into chromatin. We reveal how specialized replication-coupled mechanisms rapidly assemble newly synthesized DNA into nucleosomes, while the complete restoration of chromatin organization including histone marks is a continuous process taking place throughout the cell cycle. Because failure to reassemble nucleosomes at replication forks blocks DNA replication progression in higher eukaryotes and leads to genomic instability, we further underline the importance of the mechanistic link between DNA replication and chromatin duplication.
DNA 序列及其在染色质中的正确组织的遗传对于基因组稳定性和功能至关重要。因此，特定的染色质结构如何在新合成的 DNA 上恢复并通过细胞分裂传递仍然是理解细胞命运选择和自我更新的核心问题。在有丝分裂细胞中遗传信息和基于染色质的信息的传播需要对染色质进行全基因组的破坏和恢复，同时伴随着 DNA 的忠实复制。在本章中，我们描述了细胞如何在保持染色质正确组织的情况下复制基因组。我们揭示了专门的复制偶联机制如何快速将新合成的 DNA 组装成核小体，而包括组蛋白标记在内的染色质组织的完全恢复是一个在整个细胞周期中持续进行的过程。由于在高等真核生物中，未能在复制叉处重新组装核小体会阻止 DNA 复制的进行，并导致基因组不稳定，因此我们进一步强调了 DNA 复制和染色质复制之间的机制联系的重要性。
