Exploring the multifaceted Dbf4-dependent kinase from temporal, spatial, and substrate repertoire perspectives

Abstract

The Dbf4‑dependent kinase (DDK), composed of the catalytic subunit Cdc7 and the regulatory subunit Dbf4, is a serine/threonine kinase traditionally defined as an essential activator of DNA replication. Here, we review DDK function from three complementary perspectives: its temporal regulation during the cell cycle, its spatial organization on chromosomes, and its expanding substrate repertoire. These perspectives reveal that DDK acts beyond DNA replication, targeting proteins involved in chromosome segregation, DNA damage responses and homologous recombination. Together, they redefine DDK as multifunctional genome integrity kinase which coordinates cell cycle progression and genome stability offering a unique therapeutic potential in cancer therapy.