Aurora B prevents delayed DNA replication and premature mitotic exit by repressing p21^Cip1

Aurora kinase B is a critical component of the chromosomal passenger complex, which is involved in the regulation of microtubule-kinetochore attachments and cytokinesis. By using conditional knockout cells and chemical inhibition, we show here that inactivation of Aurora B results in delayed G ₁/S transition and premature mitotic exit. Aurora B deficiency results in delayed DNA replication in cultured fibroblasts as well as liver cells after hepatectomy. This is accompanied by increased transcription of the cell cycle inhibitor p21_Cip1. Lack of Aurora B does not prevent mitotic entry but results in a premature exit from prometaphase in the presence of increased p21^Cip1-Cdk1 inactive complexes. Aurora B-null cells display reduced degradation of cyclin B1, suggesting the presence of phenomenon known as adaptation to the mitotic checkpoint, previously described in yeast. Elimination of p21^Cip1 rescues Cdk1 activity and prevents premature mitotic exit in Aurora B-deficient cells. These results suggest that Aurora B represses p21^Cip1, preventing delayed DNA replication, Cdk inhibition and premature mitotic exit. The upregulation of p21^Cip1 observed after inhibitio of Aurora B may haves important implications in cell cycle progression, tetraploidy, senescence or cancer therapy.