Phosphorylation of the Smc4 N-Terminus Regulates DNA Binding During Condensin-Mediated Chromosome Morphogenesis in Saccharomyces cerevisiae

Abstract

Effective transmission of genetic material during mitosis has long been known to be essential for cell survival. A key mitotic regulator in eukaryotes is the condensin complex, responsible for condensing genomic DNA for its equal division between two daughter cells. Importantly, the Smc4 subunit of condensin contains an intrinsically disordered N-terminal region (Smc4-NT) unique to the Smc4 members of the conserved SMC protein family. Deletion of the entire Smc4-NT causes lethality in yeast, suggesting a unique functional role for this region. Our laboratory has previously shown that Smc4-NT phosphorylation by cyclin-dependent kinase 1 (Cdk1) at the onset of mitosis activates condensin function, but the exact role of the Smc4-NT is unknown. We have now established that the Smc4-NT has intrinsic DNA binding activity that is abrogated upon phosphorylation by Cdk1. We have also discovered that the conserved casein kinase 2 (CK2) phosphorylates the Smc4-NT in vitro and may serve to inhibit the activity of the Smc4-NT. We established the positive and negative phosphorylation of the Smc4-NT as an important regulator of condensin function.