Duronio R J, O'Farrell P H, Xie J E, Brook A, Dyson N
Department of Biochemistry and Biophysics, University of California, San Francisco 94143, USA.
Genes Dev. 1995 Jun 15;9(12):1445-55. doi: 10.1101/gad.9.12.1445.
Overexpression of the E2F-1 cDNA in mammalian cells disrupts normal control of the cell cycle and drives cells into S phase. Whereas eliminating E2F activity would test its inferred involvement in the G1-S transition, elimination is complicated by the existence of gene families encoding mammalian E2F. Here we identify mutations in a single essential Drosophila gene, dE2F, that encodes a homolog of the mammalian E2F gene family. Embryos homozygous for null mutations of dE2F complete early cell cycles, presumably using maternal contributions of gene products, but DNA synthesis falls to virtually undetectable levels in cycle 17. Mutant embryos also lack the pulses of coordinate transcription of genes encoding replication functions that usually accompany each transition from quiescence to S phase. We conclude that in most cells dE2F is essential for a G1-S transcriptional program and for G1-S progression.
E2F-1 cDNA 在哺乳动物细胞中的过表达会破坏细胞周期的正常调控，并驱使细胞进入 S 期。虽然消除 E2F 活性可以检验其在 G1-S 转换中所推断的作用，但由于存在编码哺乳动物 E2F 的基因家族，消除过程变得复杂。在这里，我们鉴定了果蝇中一个单一必需基因 dE2F 的突变，该基因编码哺乳动物 E2F 基因家族的一个同源物。dE2F 无效突变的纯合胚胎完成早期细胞周期，大概是利用基因产物的母体贡献，但在第 17 个周期中 DNA 合成降至几乎无法检测的水平。突变胚胎也缺乏通常伴随每次从静止期到 S 期转变的编码复制功能的基因的协调转录脉冲。我们得出结论，在大多数细胞中，dE2F 对于 G1-S 转录程序和 G1-S 进程至关重要。
