Cell cycle independent signaling by modified Clb5- Cdk1 complex

Abstract

A eukaryotic cell contains a robust regulatory network that controls the ordered sequence and timing of distinct cell cycle events. In budding yeast this is mainly regulated by the growing activity of cyclin-dependent kinases (Cdks) during the cell cycle. Post-translational modifications, particularly protein phosphorylation is a powerful mechanism regulating stability, localization, activity and interactions of proteins. Building synthetic circuits based on protein phosphorylation has remained a riddle due to the overlapping specificity of protein kinases. To tackle this issue it was aimed to obtain a cell cycle independent cyclin-Cdk1 input that could target substrates created specifically for this particular cyclin-Cdk1 complex. By manipulating the Cdk1 specificity of phospho-degron and -localization modules it was anticipated to design orthogonal Cdk circuits that respond to the modified Clb5-Cdk1 complex.