THE WHI1+ GENE OF SACCHAROMYCES-CEREVISIAE TETHERS CELL-DIVISION TO CELL-SIZE AND IS A CYCLIN HOMOLOG

THE WHI1+ GENE OF SACCHAROMYCES-CEREVISIAE TETHERS CELL-DIVISION TO CELL-SIZE AND IS A CYCLIN HOMOLOG
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DOI:
10.1002/j.1460-2075.1988.tb03332.x
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发表时间:
1988-12-20
期刊:
影响因子:
11.4
通讯作者:
FUTCHER, AB
FUTCHER, AB
中科院分区:
生物学1区
文献类型:
--
作者:
NASH, R;TOKIWA, G;FUTCHER, AB

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WHI 1 -1是一种显性突变,通过允许细胞以异常小的尺寸进行分裂来减少细胞体积,缩短细胞周期的G1期。该基因被克隆,剂量研究表明,正常的基因激活承诺分裂的剂量依赖性的方式,和突变基因有一个过度活跃,但定性相似的功能。轻度过度表达的突变基因消除G1期,显然完全放松正常的G1大小控制,但揭示迄今为止的神秘控制。序列分析表明,该突变体的过度活性是由野生型蛋白C-末端三分之一的丢失引起的。这部分蛋白含有PEST区域,可能是蛋白降解的信号。WHI 1蛋白与蛤细胞周期蛋白A、海胆细胞周期蛋白和裂殖酵母细胞周期蛋白同源物Cdc 13具有序列相似性。由于细胞周期蛋白是有丝分裂的诱导剂,因此WHI 1可能是分裂承诺的直接调节剂。WHI 1激活剂的可能的辅助功能是帮助从α中恢复。因子阻滞; WHI 1 -1突变细胞不能被信息素永久阻滞,这与分裂的过度激活一致。
WHI1-1 is a dominant mutation that reduces cell volume by allowing cells to commit to division at abnormally small sizes, shortening the G1 phase of the cell cycle. The gene was cloned, and dosage studies indicated that the normal gene activated commitment to division in a dose-dependent manner, and that the mutant gene had a hyperactive but qualitatively similar function. Mild over-expression of the mutant gene eliminated G1 phase, apparently entirely relaxing the normal G1 size control, but revealing hitherto cryptic controls. Sequence analysis showed that the hyperactivity of the mutant was caused by the loss of the C-terminal third of the wild-type protein. This portion of the protein contained PEST regions, which may be signals for protein degradation. The WHI1 protein had sequence similarity to clam cyclin A, to sea urchin cyclin and to Schizosaccharomyces pombe cdc13, a cyclin homolog. Since cyclins are inducers of mitosis, WHI1 may be a direct regulator of commitment to division. A probable accessory function of the WHI1 activator is to assist recovery from .alpha. factor arrest; WHI1-1 mutant cells could not be permanently arrested by pheromone, consistent with a hyperactivation of division.