The cell cycle regulation is an interplay of oscillation pattern among activities of cyclin-dependent kinase and cyclin with very distinct functions. An interesting feature within cell cycle control that was shrouded in mystery for a long time would be the necessity of higher eukaryotes requiring multiple CDK to perform functions normally while yeasts only had a single CDK to drive through G₁-S and G₂-M. With the introduction of a newly developed rapid conditional silencing system developed in my laboratory, I utilized this system to confirm the roles of CDK through different combinations in deficient of CDKs. This system was particularly useful for doing in depth investigation on essential gene CDK1 that could not survive without the gene. Not surprisingly, CDK1 was seemingly without e...[ Read more ]

The cell cycle regulation is an interplay of oscillation pattern among activities of cyclin-dependent kinase and cyclin with very distinct functions. An interesting feature within cell cycle control that was shrouded in mystery for a long time would be the necessity of higher eukaryotes requiring multiple CDK to perform functions normally while yeasts only had a single CDK to drive through G₁-S and G₂-M. With the introduction of a newly developed rapid conditional silencing system developed in my laboratory, I utilized this system to confirm the roles of CDK through different combinations in deficient of CDKs. This system was particularly useful for doing in depth investigation on essential gene CDK1 that could not survive without the gene. Not surprisingly, CDK1 was seemingly without errors to compensate the roles of the G₁-S CDK in the absence of CDK2. In reverse however, deficiency of CDK1 unexpectedly did not prevent mitotic entry relying solely on CDK2 driven catalysed mitosis. Despite the success in CDK2 to catalyse for mitosis in CDK1 deficient cells, several defects were identified throughout mitotic events. Formation of the new complex on noncanonical cyclin B-CDK2 in cells were suffering from inadequate phosphorylation of mitotic substrates and deleterious late mitotic events such as the uncoupling of anaphase A and B, and precocious cytokinesis. Intriguingly, attempts to elevate expression level of CDK2 comparable to CDK1 were seemingly able to overcome the identified defects induced due to CDK1 deficient conditions. This indicated the lower concentration of CDK2 might be accounted for the observed defects within CDK1 deficient cells. Overall, these results unveiled the critical difference between CDK1 and CDK2 in human cells might just be the quantitative differences.