One important implication of the role of CDKs in once per cell cycle replication is that the period of low CDK activity during G1 phase is critical for ensuring efficient pre-RC assembly. Experiments in budding yeast have shown that constitutive expression of a G1 cyclin (Cln2) inhibits pre-RC assembly and significantly increases gross chromosome rearrangement rates (32). We are continuing this work in budding yeast, trying to ascertain the mechanism of genome instability induced by cyclin deregulation (Anne Early).We are also examining the effect of deregulation of the analogous G1 cyclin (cyclin E) in human tissue culture cells. We are testing the hypothesis that constitutive cyclin E expression might induce a DNA damage response in human cells (Minna Makiniemi). We are very interested in the possibility that DNA damage induced by cyclin deregulation might induce cell cycle arrest or apoptosis, thus providing the drive to lose cell cycle checkpoints like p53 (see figure below).
Possible roles for cyclin deregulation in human cancer
