Medical Research Council (MRC) Laboratory for Molecular Cell Biology, University College London, London, UK.
Nat Rev Mol Cell Biol. 2013 Aug;14(8):518-28. doi: 10.1038/nrm3629.
The accurate transition from G1 phase of the cell cycle to S phase is crucial for the control of eukaryotic cell proliferation, and its misregulation promotes oncogenesis. During G1 phase, growth-dependent cyclin-dependent kinase (CDK) activity promotes DNA replication and initiates G1-to-S phase transition. CDK activation initiates a positive feedback loop that further increases CDK activity, and this commits the cell to division by inducing genome-wide transcriptional changes. G1-S transcripts encode proteins that regulate downstream cell cycle events. Recent work is beginning to reveal the complex molecular mechanisms that control the temporal order of transcriptional activation and inactivation, determine distinct functional subgroups of genes and link cell cycle-dependent transcription to DNA replication stress in yeast and mammals.
细胞周期 G1 期向 S 期的准确转换对于控制真核细胞增殖至关重要,其调控失常会促进肿瘤发生。在 G1 期,依赖于生长的细胞周期蛋白依赖性激酶(CDK)活性促进 DNA 复制并启动 G1 期向 S 期的转变。CDK 的激活引发正反馈环,进一步增加 CDK 的活性,通过诱导全基因组转录变化使细胞进入分裂状态。G1-S 转录物编码调节下游细胞周期事件的蛋白质。最近的研究工作开始揭示控制转录激活和失活的时间顺序、确定基因的不同功能亚群以及将细胞周期依赖性转录与酵母和哺乳动物中 DNA 复制应激联系起来的复杂分子机制。