Jackson P K, Chevalier S, Philippe M, Kirschner M W
Harvard Medical School, Department of Cell Biology, Boston, Massachusetts 02115, USA.
J Cell Biol. 1995 Aug;130(4):755-69. doi: 10.1083/jcb.130.4.755.
Using immunodepletion of cyclin E and the inhibitor protein p21WAF/CIP1, we demonstrate that the cyclin E protein, in association with Cdk2, is required for the elongation phase of replication on single-stranded substrates. Although cyclin E/Cdk2 is likely to be the major target by which p21 inhibits the initiation of sperm DNA replication, p21 can inhibit single-stranded replication through a mechanism dependent on PCNA. While the cyclin E/Cdk2 complex appears to have a role in the initiation of DNA replication, another Cdk kinase, possibly cyclin A/Cdk, may be involved in a later step controlling the switch from initiation to elongation. The provision of a large maternal pool of cyclin E protein shows that regulators of replication are constitutively present, which explains the lack of a protein synthesis requirement for replication in the early embryonic cell cycle.
通过细胞周期蛋白E的免疫去除和抑制蛋白p21WAF/CIP1，我们证明细胞周期蛋白E蛋白与Cdk2结合，是单链底物上复制延伸阶段所必需的。尽管细胞周期蛋白E/Cdk2可能是p21抑制精子DNA复制起始的主要靶点，但p21可通过依赖增殖细胞核抗原（PCNA）的机制抑制单链复制。虽然细胞周期蛋白E/Cdk2复合物似乎在DNA复制起始中起作用，但另一种Cdk激酶，可能是细胞周期蛋白A/Cdk，可能参与控制从起始到延伸转换的后期步骤。大量母源细胞周期蛋白E蛋白的存在表明复制调节因子是组成性存在的，这解释了早期胚胎细胞周期中复制对蛋白质合成无需求的现象。
