DBF4-dependent kinase regulatory subunit (DBF4)

DBF4 is the regulatory subunit of the Cdc7-Dbf4 kinase (DDK) complex, essential for the initiation of DNA replication during the S phase of the cell cycle. DBF4 protein levels oscillate during the cell cycle, peaking at the G1/S transition and remaining high through S and G2/M phases, thereby controlling Cdc7 kinase activity. The DBF4/Cdc7 complex phosphorylates the minichromosome maintenance (MCM) protein complex, activating it for DNA unwinding and replication fork assembly[1][2][3][4]. DBF4 is considered a promising therapeutic target in cancer due to its role in promoting cell cycle progression and DNA synthesis, and its overexpression is linked to neoplastic transformation in some tumor types[3]. Drugs that inhibit this kinase complex prevent the initiation of DNA replication, leading to cell cycle arrest and potential selective toxicity in rapidly proliferating cells[3][4].

Other names

Protein DBF4 homolog AASKDBF4AZDBF1Chiffon homolog AActivator of S phase kinaseCHIFDBF4-type zinc finger-containing protein 1

Inhibition of Cdc7-Dbf4 kinase activity, blockade of DNA replication initiation, cell cycle arrest