From Cdc2 to Cdk1

The two major processes common to all cell cycles are S phase, when chromosomes are replicated, and M phase, when the replicated chromosomes are segregated into two daughter cells. In most cell cycles, an interval of time, G1 phase, separates the previous cell division from the beginning of the next S phase. It is now firmly established that progression of the cell cycle – that is, transitions between one phase of the cycle and the next – are controlled by cyclin-dependent kinases (CDKs). This concept of a direct association between a cyclin subunit and a cell cycle kinase subunit (Cdc2) emerged from analysis of the G2/M transition. Fission yeast mutants that are prematurely advanced into mitosis and thus enter prophase at reduced size focused attention on Cdc2, but gave no clues about cyclins. In budding yeast, which are less favourable for investigation of the G2/M transition because growth occurs mainly in G1 phase, attention focused largely on the G1/S transition. Thus, paradoxically, the wealth of information about cell cycle genes in S. cerevisiae provided only a limited number of clues at first in putting cyclins together with CDKs. In contrast, efforts to purify and identify the mysterious MPF (Masui and Markert, 1971) were of paramount importance on the way to our present understanding of G2/M and, by extension, other transitions of the cell cycle. Here we look back to this heroic age and try to establish precisely when and how Cdc2 became Cdk1.