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Cyclin-specific control of ribosomal DNA segregation.

Following chromosome duplication in S phase of the cell cycle, the sister chromatids are linked by cohesin. At the onset of anaphase, separase cleaves cohesin and thereby initiates sister chromatid separation. Separase activation results from the destruction of its inhibitor, securin, which is triggered by a ubiquitin ligase called the anaphase-promoting complex (APC). Here, we show in budding yeast that securin destruction and, thus, separase activation are not sufficient for the efficient segregation of the repetitive ribosomal DNA (rDNA). We find that rDNA segregation also requires the APC-mediated destruction of the S-phase cyclin Clb5, an activator of the protein kinase Cdk1. Mutations that prevent Clb5 destruction are lethal and cause defects in rDNA segregation and DNA synthesis. These defects are distinct from the mitotic-exit defects caused by stabilization of the mitotic cyclin Clb2, emphasizing the importance of cyclin specificity in the regulation of late-mitotic events. Efficient rDNA segregation, both in mitosis and meiosis, also requires APC-dependent destruction of Dbf4, an activator of the protein kinase Cdc7. We speculate that the dephosphorylation of Clb5-specific Cdk1 substrates and Dbf4-Cdc7 substrates drives the resolution of rDNA in early anaphase. The coincident destruction of securin, Clb5, and Dbf4 coordinates bulk chromosome segregation with segregation of rDNA.

Pubmed ID: 18591250

Authors

  • Sullivan M
  • Holt L
  • Morgan DO

Journal

Molecular and cellular biology

Publication Data

September 15, 2008

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM069901

Mesh Terms

  • Anaphase-Promoting Complex-Cyclosome
  • Chromosome Segregation
  • Cyclin B
  • DNA Replication
  • DNA, Ribosomal
  • Meiosis
  • Models, Biological
  • Mutation
  • Protein Processing, Post-Translational
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin-Protein Ligase Complexes