Noguchi Eishi, Shanahan Paul, Noguchi Chiaki, Russell Paul
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Curr Biol. 2002 Apr 2;12(7):599-605. doi: 10.1016/s0960-9822(02)00739-x.
Cyclin-dependent kinases (CDKs) are absolutely required for DNA replication in eukaryotic cells. CDKs are thought to activate one or more replication factors, but the identities of these proteins are unknown. Here we describe fission yeast Drc1, a protein required for DNA replication that is phosphorylated by Cdc2. Drc1 depletion leads to catastrophic mitotic divisions with incompletely replicated DNA, indicating that Drc1 is required for DNA synthesis and S-M replication checkpoint control. Drc1 associates with Cdc2 and is phosphorylated at the onset of S phase when Cdc2 is activated. Mutant Drc1 that lacks CDK phosphorylation sites is nonfunctional and fails to interact with Cut5 replication factor. These data suggest that Cdc2 promotes DNA replication by phosphorylating Drc1 and regulating its association with Cut5.
细胞周期蛋白依赖性激酶（CDK）是真核细胞中DNA复制绝对必需的。人们认为CDK可激活一种或多种复制因子，但这些蛋白质的具体身份尚不清楚。在此，我们描述了裂殖酵母Drc1，一种DNA复制所需的蛋白质，它被Cdc2磷酸化。Drc1缺失会导致有丝分裂灾难性分裂，DNA复制不完全，这表明Drc1是DNA合成和S-M复制检查点控制所必需的。Drc1与Cdc2结合，并在S期开始Cdc2被激活时被磷酸化。缺乏CDK磷酸化位点的突变型Drc1无功能，且无法与Cut5复制因子相互作用。这些数据表明，Cdc2通过磷酸化Drc1并调节其与Cut5的结合来促进DNA复制。
