CDK1 and CK2 Phosphorylation of the Smc4-IDR Modulate Condensin Function in Saccharomyces cerevisae

Abstract

Effective chromosome condensation and segregation require controlled condensin activity, mediated in part by post-translational modification. In Saccharomyces cerevisiae, Smc4 N-terminal intrinsically disordered region (IDR) phosphorylation by CDK1 and CK2 regulate condensin-chromatin interactions. This study used alanine-replacement mutants to examine Smc4-IDR phosphorylation function. CK2 phospho-mutants smc4-9CK2 and smc4-13CK2 exhibited wild type-like segregation of sister chromatids but reduced rDNA copy number, revealing altered nucleolar maintenance. CDK1 phospho-mutant smc4-7CDK1 exhibited severe condensation defects. Surprisingly, double mutants smc4-16CDK1/CK2 and smc4-20CDK1/CK2 rescued smc4-7CDK1 viability and segregation with compromised rDNA morphology and copy number. Reducing CK2 activity in smc4-7CDK1 ckb1∆ ckb2∆ confirmed CK2's role in this rescue. Quantitative assays detected compact, loop-deficient chromatin in rescued strains, suggesting a model whereby Smc4-IDR phosphorylation influences condensin activity as well as its preference to engage in loop-extrusion or cross-linking of DNA. These findings suggest that CDK1 and CK2 together regulate condensin to coordinate mitotic fidelity and temporal chromatin organization.