Sclafani R A, Holzen T M
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Annu Rev Genet. 2007;41:237-80. doi: 10.1146/annurev.genet.41.110306.130308.
Eukaryotic DNA replication is regulated to ensure all chromosomes replicate once and only once per cell cycle. Replication begins at many origins scattered along each chromosome. Except for budding yeast, origins are not defined DNA sequences and probably are inherited by epigenetic mechanisms. Initiation at origins occurs throughout the S phase according to a temporal program that is important in regulating gene expression during development. Most replication proteins are conserved in evolution in eukaryotes and archaea, but not in bacteria. However, the mechanism of initiation is conserved and consists of origin recognition, assembly of prereplication (pre-RC) initiative complexes, helicase activation, and replisome loading. Cell cycle regulation by protein phosphorylation ensures that pre-RC assembly can only occur in G1 phase, whereas helicase activation and loading can only occur in S phase. Checkpoint regulation maintains high fidelity by stabilizing replication forks and preventing cell cycle progression during replication stress or damage.
真核生物的DNA复制受到调控，以确保所有染色体在每个细胞周期中只复制一次且仅复制一次。复制起始于沿每条染色体分散分布的多个起点。除了芽殖酵母外，起点不是特定的DNA序列，可能通过表观遗传机制遗传。根据一个在发育过程中调节基因表达很重要的时间程序，起点处的起始在整个S期都会发生。大多数复制蛋白在真核生物和古细菌的进化过程中是保守的，但在细菌中则不然。然而，起始机制是保守的，包括起点识别、复制前（pre-RC）起始复合物的组装、解旋酶激活和复制体加载。通过蛋白质磷酸化进行的细胞周期调控确保pre-RC组装只能在G1期发生，而解旋酶激活和加载只能在S期发生。检查点调控通过稳定复制叉并在复制应激或损伤期间阻止细胞周期进程来维持高保真度。
