Dong X, Zavitz K H, Thomas B J, Lin M, Campbell S, Zipursky S L
Department of Biological Chemistry, Molecular Biology Institute, University of California, Los Angeles 90095, USA.
Genes Dev. 1997 Jan 1;11(1):94-105. doi: 10.1101/gad.11.1.94.
In the developing eye of Drosophila melanogaster, cells become synchronized in the G1 phase of the cell cycle just prior to the onset of cellular differentiation and morphogenesis. In roughex (rux) mutants, cells enter S phase precociously because of ectopic activation of a Cyclin A/Cdk complex in early G1. This leads to defects in cell fate and pattern formation, and results in abnormalities in the morphology of the adult eye. A screen for dominant suppressors of the rux eye phenotype led to the identification of mutations in cyclin A, string (cdc25), and new cell cycle genes. One of these genes, regulator of cyclin A (rca1), encodes a novel protein required for both mitotic and meiotic cell cycle progression. rca1 mutants arrest in G2 of embryonic cell cycle 16 with a phenotype very similar to cyclin A loss of function mutants. Expression of rca1 transgenes in G1 or in postmitotic neurons promotes Cyclin A protein accumulation and drives cells into S phase in a Cyclin A-dependent fashion.
在黑腹果蝇发育中的眼睛里,细胞在细胞分化和形态发生开始之前,会在细胞周期的G1期实现同步化。在粗糙眼(rux)突变体中,由于细胞周期蛋白A/周期蛋白依赖性激酶(Cdk)复合物在G1早期的异位激活,细胞会过早进入S期。这会导致细胞命运和模式形成出现缺陷,并导致成年果蝇眼睛形态异常。对rux眼表型的显性抑制子进行筛选,从而鉴定出细胞周期蛋白A、纺锤体(cdc25)和新的细胞周期基因中的突变。其中一个基因,细胞周期蛋白A调节因子(rca1),编码一种有丝分裂和减数分裂细胞周期进程都需要的新型蛋白质。rca1突变体在胚胎细胞周期16的G2期停滞,其表型与细胞周期蛋白A功能缺失突变体非常相似。在G1期或有丝分裂后神经元中表达rca1转基因,可促进细胞周期蛋白A的蛋白质积累,并以细胞周期蛋白A依赖性方式驱使细胞进入S期。