ARTICLE

Correct execution of mitosis in eukaryotes relies on timely activation and inactivation of cyclin B-dependent kinase 1 (cdk1), the m-phase-promoting factor (mPF). once activated, mPF is sustained until mitotic spindle assembly by phosphorylation-dependent feedback loops that prevent inhibitory phosphorylation of cdk1 and ubiquitin-dependent degradation of cyclin B. Whether subsequent mPF inactivation and anaphase onset require a specific phosphatase(s) to reverse these feedback loops is not known. Here we show through biochemical and genetic evidence that timely mPF inactivation requires activity of the essential RnA polymerase II-carboxy-terminal domain phosphatase Fcp1, in a transcription-independent manner. We identify Cdc20, a coactivator of the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) required for cyclin degradation and anaphase onset, usP44, a deubiquitinating peptidase that opposes APC/C action, and Wee1, a cdk1 inhibitory kinase, as relevant Fcp1 targets. We propose that Fcp1 has a crucial role in the liaison between dephosphorylation and ubiquitination that drives mitosis exit