Deregulated G1-cyclin expression induces genomic instability by preventing efficient pre-RC formation

Genes and Development - Tập 16 Số 20 - Trang 2639-2649 - 2002
Seiji Tanaka1, John F.X. Diffley
1Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.

Tóm tắt

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.

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