Bailis Julie M, Forsburg Susan L
Molecular and Cell Biology Laboratory, The Salk Institute, La Jolla, California, USA.
Cell Cycle. 2003 Jul-Aug;2(4):303-6.
Many aspects of chromosome biology are fundamentally linked to events that occur during the DNA synthesis (S) phase of the cell cycle. The DNA must be duplicated once, and once exactly, each S phase. Local chromatin structure must also be re-assembled each S phase to incorporate newly replicated sister chromatids. The replication fork is the one complex that potentially interacts with every nucleotide of the genome, providing a mechanism to couple chromatin assembly to S phase passage. Importantly, eukaryotic genomes contain regions of structurally distinct chromatin, such as heterochromatin, defined by distinct patterns of histone modification and specific protein associations. Heterochromatin is generally associated with repeated sequence elements near centromeres, telomeres and other sites. Evidence suggests that heterochromatin assembled during S phase supports the association of multiprotein complexes required for many chromosome transactions, including transcriptional silencing, sister-chromatid cohesion, and kinetochore function. These complexes are in turn essential for regulated gene expression, equal chromosome segregation and genomic stability. Intriguingly, recent studies indicate that these processes are linked to S phase by temporal mechanisms as well as by replication-dependent activities.
染色体生物学的许多方面都与细胞周期的DNA合成(S)期发生的事件有着根本联系。每个S期,DNA必须精确复制一次。每个S期还必须重新组装局部染色质结构,以纳入新复制的姐妹染色单体。复制叉是唯一可能与基因组的每个核苷酸相互作用的复合体,提供了一种将染色质组装与S期进程相耦合的机制。重要的是,真核生物基因组包含结构上不同的染色质区域,如异染色质,由不同的组蛋白修饰模式和特定的蛋白质结合所定义。异染色质通常与着丝粒、端粒和其他位点附近的重复序列元件相关。有证据表明,S期组装的异染色质支持许多染色体活动所需的多蛋白复合体的结合,包括转录沉默、姐妹染色单体黏连和动粒功能。这些复合体对于调控基因表达、染色体均等分离和基因组稳定性至关重要。有趣的是,最近的研究表明,这些过程通过时间机制以及依赖复制的活动与S期相联系。