G1 期细胞周期蛋白表达失调通过阻止有效的前复制复合体形成诱导基因组不稳定。
Deregulated G1-cyclin expression induces genomic instability by preventing efficient pre-RC formation.
作者信息
Tanaka Seiji, Diffley John F X
机构信息
Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.
出版信息
Genes Dev. 2002 Oct 15;16(20):2639-49. doi: 10.1101/gad.1011002.
Abstract
Although genomic instability is a hallmark of human cancer cells, the mechanisms by which genomic instability is generated and selected for during oncogenesis remain obscure. In most human cancers, the pathway leading to the activation of the G1 cyclins is deregulated. Using budding yeast as a model, we show that overexpression of the G1 cyclin Cln2 inhibits the assembly of prereplicative complexes (pre-RCs) and induces gross chromosome rearrangements (GCR). Our results suggest that deregulation of G1 cyclins, selected for in oncogenesis because it confers clonal growth advantage, may also provide an important mechanism for generating genomic instability by inhibiting replication licensing.
摘要
尽管基因组不稳定是人类癌细胞的一个标志，但在肿瘤发生过程中基因组不稳定产生和被选择的机制仍不清楚。在大多数人类癌症中，导致G1期细胞周期蛋白激活的途径失调。以芽殖酵母为模型，我们发现G1期细胞周期蛋白Cln2的过表达会抑制复制前复合体（pre-RC）的组装，并诱导大规模染色体重排（GCR）。我们的结果表明，G1期细胞周期蛋白的失调在肿瘤发生过程中因赋予克隆生长优势而被选择，它也可能通过抑制复制许可为产生基因组不稳定提供一个重要机制。
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