Tsurimoto T
Faculty of Bioscience, Nara Institute of Science and Technology, Takayama, Ikoma 630-0101, Japan.
Front Biosci. 1999 Dec 1;4:D849-58. doi: 10.2741/tsurimoto.
PCNA (proliferating cell nuclear antigen), originally characterized as a DNA polymerase accessory protein, functions as a DNA sliding clamp for DNA polymerase delta and is an essential component for eukaryotic chromosomal DNA replication. Recent studies have revealed a striking feature of PCNA in its ability to interact with multiple partners, involved, for example, in Okazaki fragment joining, DNA repair, DNA methylation and chromatin assembly. Since these reactions take place mainly on replicating DNA, PCNA has applications as a marker for DNA synthesis. It is of interest that proteins involved in cell cycle regulation may also exhibit PCNA binding activity. For example, the CDK inhibitor, p21 (Cip1/Waf1) interacts with PCNA blocking its activity necessary for DNA replication and also affecting interactions with other PCNA binding proteins. The available data indicate that DNA sliding clamps have generated additional functions with evolution of eukaryotes from simple prokaryotes. In mammalian cells, they play key roles in controlling DNA synthesis reactions and the reorganization of replicated DNA at replication forks. Several cell cycle regulation proteins target these processes by affecting PCNA actions
增殖细胞核抗原(PCNA)最初被鉴定为一种DNA聚合酶辅助蛋白,作为DNA聚合酶δ的DNA滑动夹发挥作用,是真核染色体DNA复制的必需成分。最近的研究揭示了PCNA的一个显著特征,即它能够与多个伙伴相互作用,例如参与冈崎片段连接、DNA修复、DNA甲基化和染色质组装。由于这些反应主要发生在复制的DNA上,PCNA可作为DNA合成的标志物。有趣的是,参与细胞周期调控的蛋白质也可能表现出PCNA结合活性。例如,CDK抑制剂p21(Cip1/Waf1)与PCNA相互作用,阻断其DNA复制所需的活性,并影响与其他PCNA结合蛋白的相互作用。现有数据表明,随着真核生物从简单的原核生物进化而来,DNA滑动夹产生了额外的功能。在哺乳动物细胞中,它们在控制DNA合成反应以及复制叉处复制DNA的重组中发挥关键作用。几种细胞周期调控蛋白通过影响PCNA的作用来靶向这些过程。