Maiorano D, Van Assendelft G B, Kearsey S E
Department of Zoology, University of Oxford, UK.
EMBO J. 1996 Feb 15;15(4):861-72.
The fission yeast cdc21 protein belongs to the MCM family, implicated in the once per cell cycle regulation of chromosome replication. In budding yeast, proteins in this family are eliminated from the nucleus during S phase, which has led to the suggestion that they may serve to distinguish unreplicated from replicated DNA, as in the licensing factor model. We show here that, in contrast to the situation in budding yeast, cdc21 remains in the nucleus after S phase, as is found for related proteins in mammalian cells. We suggest that regulation of nuclear import of these proteins may not be an essential aspect of their function in chromosome replication. To determine the function of cdc21+, we have analysed the phenotype of a gene deletion. cdc21+ is required for entry into S phase and, unexpectedly, a proportion of cells depleted of the gene product are able to enter mitosis in the absence of DNA replication. These results are consistent with the view that individual proteins in the MCM family are required for all initiation events, and defective initiation may impair the coordination between mitosis and S phase.
裂殖酵母的cdc21蛋白属于MCM家族,参与细胞周期中染色体复制的单次调控。在芽殖酵母中,该家族的蛋白质在S期从细胞核中消失,这使人推测它们可能像在执照因子模型中一样,用于区分未复制的DNA和已复制的DNA。我们在此表明,与芽殖酵母的情况相反,cdc21在S期后仍保留在细胞核中,哺乳动物细胞中的相关蛋白质也是如此。我们认为,这些蛋白质的核输入调控可能不是其在染色体复制中功能的关键方面。为了确定cdc21+的功能,我们分析了基因缺失的表型。进入S期需要cdc21+,出乎意料的是,一部分缺乏该基因产物的细胞在没有DNA复制的情况下能够进入有丝分裂。这些结果与以下观点一致,即MCM家族中的单个蛋白质是所有起始事件所必需的,起始缺陷可能会损害有丝分裂和S期之间的协调。