Cdc7p-Dbf4p becomes famous in the cell cycle - Commentary

Great insight into the molecular details of cell cycle regulation has been obtained in the past decade. However, most of the progress has been in defi ning the regulation of the family of cyclin-dependent kinases (CDKs). Recen t studies of a myriad of eukaryotic organisms have defined both the regulat ion and substrates of Cdc7p kinase, which forms a CDK-cyclin-like complex w ith Dbf4p, is necessary for the initiation of DNA replication and has been conserved in evolution, This kinase is also required for the induction of m utations after DNA damage and for commitment to recombination in the meioti c eel cycle. However, less is known about the role of the kinase in these p rocesses. In a manner similar to CDKs, Cdc7p is activated by a regulatory s ubunit, Dbf4, the levels of which fluctuate during the cell cycle. One or m ore subunits of the conserved MCM helicase complex at chromosomal origins o f DNA replication are substrates for the kinase during S phase. Phosphoryla tion of the MCM complex by Cdc7p-Dbf4p might activate DNA replication by un winding DNA, Therefore, activation of Cdc7p is required for DNA replication , Given that Cdc7p-Dbf4 kinase is overexpressed in many neoplastic cells an d tumors, it might be an important early biomarker during cancer progressio n.