Cheng L, Collyer T, Hardy C F
Department of Cell Biology and Physiology and Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Mol Cell Biol. 1999 Jun;19(6):4270-8. doi: 10.1128/MCB.19.6.4270.
The precise duplication of eukaryotic genetic material takes place once and only once per cell cycle and is dependent on the completion of the previous mitosis. Two evolutionarily conserved kinases, the cyclin B (Clb)/cyclin-dependent kinase (Cdk/Cdc28p) and Cdc7p along with its interacting factor Dbf4p, are required late in G1 to initiate DNA replication. We have determined that the levels of Dbf4p are cell cycle regulated. Dbf4p levels increase as cells begin S phase and remain high through late mitosis, after which they decline dramatically as cells begin the next cell cycle. We report that Dbf4p levels are sensitive to mutations in key components of the anaphase-promoting complex (APC). In addition, Dbf4p is modified in response to DNA damage, and this modification is dependent upon the DNA damage response pathway. We had previously shown that Dbf4p interacts with the M phase polo-like kinase Cdc5p, a key regulator of the APC late in mitosis. These results further link the actions of the initiator protein, Dbf4p, to the completion of mitosis and suggest possible roles for Dbf4p during progression through mitosis.
真核生物遗传物质的精确复制在每个细胞周期中发生一次且仅发生一次，并依赖于前一次有丝分裂的完成。两种在进化上保守的激酶，即细胞周期蛋白B（Clb）/细胞周期蛋白依赖性激酶（Cdk/Cdc28p）和Cdc7p及其相互作用因子Dbf4p，在G1期晚期是启动DNA复制所必需的。我们已经确定Dbf4p的水平受细胞周期调控。随着细胞开始进入S期，Dbf4p水平升高，并在有丝分裂后期一直保持较高水平，之后随着细胞开始下一个细胞周期，其水平急剧下降。我们报告称，Dbf4p水平对后期促进复合物（APC）关键成分的突变敏感。此外，Dbf4p会因DNA损伤而发生修饰，且这种修饰依赖于DNA损伤反应途径。我们之前曾表明，Dbf4p与M期polo样激酶Cdc5p相互作用，Cdc5p是有丝分裂后期APC的关键调节因子。这些结果进一步将起始蛋白Dbf4p的作用与有丝分裂的完成联系起来，并暗示了Dbf4p在有丝分裂进程中的可能作用。
