Phosphorylation of the Scc2 cohesin deposition complex subunit regulates chromosome condensation through cohesin integrity
| Autor: | Matthew G. Hoffman, Paul C. Megee, Julie Woodman, Monika Dzieciatkowska, Kirk C. Hansen |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Cohesin complex DNA Repair Chromosomal Proteins Non-Histone Cell Cycle Proteins Saccharomyces cerevisiae Biology Chromatids Chromosomes Mass Spectrometry Chromosome segregation Chromosome Segregation Sister chromatids Phosphorylation Molecular Biology Mitosis Cohesin Kinetochore Cell Cycle Cell Biology Articles Molecular biology Chromatin Cell biology Premature chromosome condensation Separase biological phenomena cell phenomena and immunity |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 |
| Popis: | Cohesin deposition requires the Scc2/Scc4 complex. Scc2 is phosphorylated, and mutations that mimic constitutive phosphorylation lead to inviability and chromosome condensation defects, likely due to reduced Mcd1 levels resulting from compromised cohesin integrity. Thus phosphoregulation of Scc2 has important consequences for chromosome integrity. The cohesion of replicated sister chromatids promotes chromosome biorientation, gene regulation, DNA repair, and chromosome condensation. Cohesion is mediated by cohesin, which is deposited on chromosomes by a separate conserved loading complex composed of Scc2 and Scc4 in Saccharomyces cerevisiae. Although it is known to be required, the role of Scc2/Scc4 in cohesin deposition remains enigmatic. Scc2 is a phosphoprotein, although the functions of phosphorylation in deposition are unknown. We identified 11 phosphorylated residues in Scc2 by mass spectrometry. Mutants of SCC2 with substitutions that mimic constitutive phosphorylation retain normal Scc2–Scc4 interactions and chromatin association but exhibit decreased viability, sensitivity to genotoxic agents, and decreased stability of the Mcd1 cohesin subunit in mitotic cells. Cohesin association on chromosome arms, but not pericentromeric regions, is reduced in the phosphomimetic mutants but remains above a key threshold, as cohesion is only modestly perturbed. However, these scc2 phosphomimetic mutants exhibit dramatic chromosome condensation defects that are likely responsible for their high inviability. From these data, we conclude that normal Scc2 function requires modulation of its phosphorylation state and suggest that scc2 phosphomimetic mutants cause an increased incidence of abortive cohesin deposition events that result in compromised cohesin complex integrity and Mcd1 turnover. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|