CDC46/MCM5, A YEAST PROTEIN WHOSE SUBCELLULAR-LOCALIZATION IS CELL CYCLE-REGULATED, IS INVOLVED IN DNA-REPLICATION AT AUTONOMOUSLY REPLICATING SEQUENCES
CDC46/MCM5, A YEAST PROTEIN WHOSE SUBCELLULAR-LOCALIZATION IS CELL CYCLE-REGULATED, IS INVOLVED IN DNA-REPLICATION AT AUTONOMOUSLY REPLICATING SEQUENCES
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DOI：
10.1073/pnas.89.21.10459
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发表时间：
1992-11-01
影响因子：
11.1
通讯作者：
TYE, BK
中科院分区：
文献类型：
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作者：
CHEN, YR;HENNESSY, KM;TYE, BK
在非允许的温度下，细胞分裂周期基因CDC 46中含有突变的酿酒酵母细胞以大芽和具有未复制DNA的单核停滞。这种G1/S停滞，以及有丝分裂染色体丢失和重组表型的增加，表明这些突变体在DNA复制中有缺陷。CDC 46蛋白的亚细胞定位随细胞周期而变化;在M期结束和G1/S转换之间是核内的，但在细胞周期的其他阶段是胞质内的。在这里，我们表明，CDC 46是相同的MCM 5，基于互补分析的MCM 5 -1和cdc 46 -1等位基因，互补的微小染色体维持缺陷的MCM 5 -1的CDC 46，和这两个基因的遗传连锁。与mcm 5 -1一样，cdc 46 -1和cdc 46 -5也显示出被认为与自主复制序列处的DNA复制起始相关的微型染色体维持缺陷。综上所述，这些观察结果表明，CDC 46/MCM 5在G1/S转换或S期开始时的非常窄的窗口期间，凭借其核定位来影响自主复制序列处的DNA复制的起始。
Saccharomyces cerevisiae cells containing mutations in the cell-division-cycle gene CDC46 arrest with a large bud and a single nucleus with unreplicated DNA at the non-permissive temperature. This G1/S arrest, together with the increased rates of mitotic chromosome loss and recombination phenotype, suggests that these mutants are defective in DNA replication. The subcellular localization of the CDC46 protein changes with the cell cycle; it is nuclear between the end of M phase and the G1/S transition but is cytoplasmic in other phases of the cell cycle. Here we show that CDC46 is identical to MCM5, based on complementation analysis of the mcm5-1 and cdc46-1 alleles, complementation of the minichromosome maintenance defect of mcm5-1 by CDC46, and the genetic linkage of these two genes. Like mcm5-1, cdc46-1 and cdc46-5 also show a minichromosome maintenance defect thought to be associated with DNA replication initiation at autonomously replicating sequences. Taken together, these observations suggest that CDC46/MCM5 acts during a very narrow window at the G1/S transition or the beginning of S phase by virtue of its nuclear localization to effect the initiation of DNA replication at autonomously replicating sequences.