Cecilia Claudi

Proper chromosome segregation requires an orderly sequence of events, whereby spindle elongation follows the dissolution of sister chromatid linkages. The mitotic spindle is a sophisticated and complex machinery built of microtubules, microtubule associated proteins and motor proteins. Proper spindle function requires that microtubule dynamics are stabilized at anaphase. This change in microtubule dynamics is dictated by a shift in the balance of kinase and phosphatase activities in favor of the phosphatases. The finding that cells simultaneously lacking the polo-like kinase Cdc5 and the phosphatase Cdc14 cannot progress through anaphase albeit having cleaved cohesin due to defects in spindle elongation, challenges the view of mitotic exit as a time for protein dephosphorylation.

We identified the kinesin 5 motor protein Cin8 as a key target of the “Cdc14-Cdc5” spindle elongation pathway. We show that besides being dephosphorylated by Cdc14, Cin8 is also phosphorylated by Cdc5 on residues S409 and S441, and that this phosphorylation is crucial for the function of the kinesin in anaphase spindle elongation. The finding that Cin8 is simultaneously a substrate of a kinase and a phosphatase sheds light on the complexity of mitotic exit regulation. Since it appears that phosphorylation and dephosphorylation events are equally important to the point that kinases and phosphatases cooperate to regulate the same substrates, the view of mitotic exit as the realm of phosphatases is dismantled and the continuous need for single molecule studies in addition to global analyses investigation is put forward.