Cdc7l1
Abstract
Cdc7 (Cell division cycle 7), also known as Hsk1 in fission yeast, is an important serine/threonine kinase, whose sequence is conserved from yeasts to mammals. The kinase activity of Cdc7 is regulated during the cell cycle by an activation subunit Dbf4 (also known as Dfp1/Him1 in fission yeast and ASK in mammals,) via heterodimer formation between the two. Cdc7 was first identified in budding yeast as a temperature-sensitive mutant (cdc7 ts ) defective in cell cycle progression. The budding yeast cdc7 ts cells arrest immediately before the onset of S phase at the non-permissive temperature, but resume growth and complete S phase in the absence of ongoing protein synthesis upon return to the permissive temperature. Cdc7 plays a conserved, pivotal role in triggering origin firing through phosphorylation of MCM (mini-chromosome maintenance) proteins. It facilitates the loading of Cdc45 and other replisome factors onto the pre-replicative complex, to generate active replication forks. In addition, it regulates other chromosomal transactions including DNA damage checkpoint, meiotic recombination, bypass DNA synthesis and histone functions. Selective induction of apoptosis in human cancer cells, but not in normal fibroblasts, after Cdc7 inhibition has provoked the effort in the development of Cdc7 inhibitors as potential anti-cancer drugs. Indeed, studies to date have suggested human Cdc7 as a new promising target in cancer therapy.