Genome Stability Unit, London Research Institute, Clare Hall Laboratories, South Mimms, Herts, UK.
Cell Cycle. 2010 Sep 15;9(18):3662-6. doi: 10.4161/cc.9.18.13060. Epub 2010 Sep 16.
Chromosomal DNA must be precisely replicated in each cell cycle in order to ensure maintenance of genome stability. Most of the factors controlling this process have been identified in lower eukaryotes. Several factors involved in DNA replication are also important for the cellular response to stress conditions. However, the regulation of DNA replication in multi-cellular organisms is still poorly understood. Using the Xenopus laevis egg cell-free system, we have recently identified a novel vertebrate protein named GEMC1 required for DNA replication. xGEMC1 is a Cyclin dependent kinase (CDK) target required forCdc45 loading onto chromatin and it interacts with the checkpoint and replication factor TopBP1, which promotes its binding to chromatin during prereplication complex formation. Here we discuss our recent findings and propose possible roles for GEMC1. Interestingly, recent studies have identified other proteins with analogous functions, showing a higher level of complexity in metazoan replication control compared to lower eukaryotes.
为了确保基因组稳定性,染色体 DNA 必须在每个细胞周期中精确复制。控制这一过程的大多数因素在较低等真核生物中已被鉴定出来。参与 DNA 复制的几个因素对于细胞对应激条件的反应也很重要。然而,多细胞生物中 DNA 复制的调控仍知之甚少。我们最近使用非洲爪蟾卵无细胞系统,鉴定了一种新的脊椎动物蛋白 GEMC1,它是 DNA 复制所必需的。xGEMC1 是周期蛋白依赖性激酶 (CDK) 的靶标,对于 Cdc45 加载到染色质上是必需的,它与检查点和复制因子 TopBP1 相互作用,促进其在复制前复合物形成过程中与染色质结合。在这里,我们讨论我们最近的发现,并提出 GEMC1 可能的作用。有趣的是,最近的研究已经鉴定出其他具有类似功能的蛋白质,表明真核生物的复制控制比较低等真核生物具有更高的复杂性。