AURKB/Ipl1 restarts replication forks to recover from replication stress

Abstract

AbstractAurora kinase B (AURKB in human, Ipl1 in S. cerevisiae) is a master regulator of mitosis and its dysregulation has been implicated in chromosome instability. AURKB accumulates in the nucleus in S-phase and is regulated by CHK1 but has not been implicated in in the DNA Damage Response (DDR). Here we show that AURKB has a conserved role to recover from replication stress and restart replication forks. Active AURKB is localized to replication forks after a prolonged arrest. CHK1 phosphorylation of AURKB induces activating phosphorylation of PLK1 and both Aurora and Plk1 are required to deactivate the DDR. Clinical trials with AURKB inhibitors are designed to target established roles for AURKB in mitosis. Our data suggest combinations of AURKB inhibitors and DNA damaging agents could be of therapeutic importance.