Paidhungat M, Garrett S
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Genetics. 1998 Apr;148(4):1777-86. doi: 10.1093/genetics/148.4.1777.
Cdc1 function was initially implicated in bud formation and nuclear division because cdc1(Ts) cells arrested with a small bud, duplicated DNA, and undivided nucleus. Our studies show that Cdc1 is necessary for cell growth at several stages of the cell cycle, as well as in pheromone-treated cells. Thus, Cdc1 depletion might affect bud formation and nuclear division, as well as other cellular processes, by blocking a process involved in general cell growth. Cells depleted of intracellular Mn2+ also exhibit a cdc1-like phenotype and recent results suggested Cdc1 might be a Mn2+-dependent protein. We show that all of the conditional Cdc1(Ts) alleles tested cause cells to become sensitive to Mn2+ depletion. In addition, Cdc1 overproduction alleviates the chelator sensitivity of several Mn2+ homeostasis mutants. These findings are compatible with a model in which Cdc1 regulates intracellular, and in particular cytosolic, Mn2+ levels which, in turn, are necessary for cell growth.
Cdc1的功能最初被认为与芽的形成和核分裂有关,因为cdc1(温度敏感型)细胞会停滞在形成小芽、DNA复制但细胞核未分裂的阶段。我们的研究表明,Cdc1在细胞周期的几个阶段以及在信息素处理的细胞中对细胞生长都是必需的。因此,Cdc1的缺失可能通过阻断一个参与一般细胞生长的过程来影响芽的形成、核分裂以及其他细胞过程。细胞内Mn2+缺失的细胞也表现出类似cdc1的表型,最近的结果表明Cdc1可能是一种依赖Mn2+的蛋白质。我们发现,所有测试的条件性Cdc1(温度敏感型)等位基因都会使细胞对Mn2+缺失变得敏感。此外,Cdc1的过量表达减轻了几种Mn2+稳态突变体对螯合剂的敏感性。这些发现与一个模型相符,即Cdc1调节细胞内特别是胞质中的Mn2+水平,而这反过来又是细胞生长所必需的。