Division of Biology 147-75, California Institute of Technology, Pasadena, CA 91125, USA.
Cell. 2010 Feb 5;140(3):349-59. doi: 10.1016/j.cell.2009.12.049. Epub 2010 Jan 28.
TopBP1 has important roles in both DNA replication and checkpoint regulation in vertebrates. We have identified a protein called Treslin that associates with TopBP1 in Xenopus egg extracts. Depletion of Treslin from egg extracts strongly inhibits chromosomal DNA replication. Binding of Treslin to chromatin in egg extracts occurs independently of TopBP1. However, loading of the initiator protein Cdc45 onto chromatin cannot take place in the absence of Treslin. Prior to the initiation of DNA replication, Treslin associates with TopBP1 in a Cdk2-dependent manner. Ablation of Treslin from human cells also strongly inhibits DNA replication. Taken together, these results indicate that Treslin and TopBP1 collaborate in the Cdk2-mediated loading of Cdc45 onto replication origins. Thus, Treslin regulates a pivotal step in the initiation of DNA replication in vertebrates.
TopBP1 在脊椎动物的 DNA 复制和检查点调节中都具有重要作用。我们已经鉴定出一种名为 Treslin 的蛋白质，它与 Xenopus 卵提取物中的 TopBP1 相关联。从卵提取物中耗尽 Treslin 会强烈抑制染色体 DNA 复制。Treslin 在卵提取物中的染色质结合独立于 TopBP1。然而，起始蛋白 Cdc45 在没有 Treslin 的情况下不能加载到染色质上。在 DNA 复制开始之前，Treslin 以 Cdk2 依赖性的方式与 TopBP1 相关联。从人细胞中剔除 Treslin 也强烈抑制 DNA 复制。总之，这些结果表明 Treslin 和 TopBP1 在 Cdk2 介导的 Cdc45 加载到复制起点上协作。因此，Treslin 调节脊椎动物 DNA 复制起始的关键步骤。
