Pre-anaphase chromosome oscillations are regulated by the antagonistic activities of Cdk1 and PP1 on Kif18A

Abstract

Upon congression at the spindle equator, vertebrate chromosomes display oscillatory movements which typically decline as cells progress towards anaphase. Kinesin-8 ​Kif18A has been identified as a suppressor of chromosome movements, but how its activity is temporally regulated to dampen chromosome oscillations before anaphase onset remained mysterious. Here, we identify a regulatory network composed of ​cyclin-dependent kinase-1 (​Cdk1) and protein phosphatase-1 (PP1) that antagonistically regulate ​Kif18A. ​Cdk1-mediated inhibitory phosphorylation of ​Kif18A promotes chromosome oscillations in early metaphase. PP1 induces metaphase plate thinning by directly dephosphorylating ​Kif18A. Chromosome attachment induces ​Cdk1 inactivation and kinetochore recruitment of ​PP1α/γ. Thus, we propose that chromosome biorientation mediates the alignment of chromosomes at the metaphase plate by tipping the balance in favour of dephosphorylated ​Kif18A capable of suppressing the oscillatory movements of chromosomes. Notably, interfering with chromosome oscillations severely impairs the fidelity of sister chromatid segregation demonstrating the importance of timely controlled chromosome dynamics for the maintenance of genome integrity.