Degradation of a cohesin subunit by the N-end rule pathway is essential for chromosome stability

Nature. 2001 Apr 19;410(6831):955-9. doi: 10.1038/35073627.


Cohesion between sister chromatids is established during DNA replication and depends on a protein complex called cohesin. At the metaphase-anaphase transition in the yeast Saccharomyces cerevisiae, the ESP1-encoded protease separin cleaves SCC1, a subunit of cohesin with a relative molecular mass of 63,000 (Mr 63K). The resulting 33K carboxy-terminal fragment of SCC1 bears an amino-terminal arginine-a destabilizing residue in the N-end rule. Here we show that the SCC1 fragment is short-lived (t1/2 approximately 2 min), being degraded by the ubiquitin/proteasome-dependent N-end rule pathway. Overexpression of a long-lived derivative of the SCC1 fragment is lethal. In ubr1Delta cells, which lack the N-end rule pathway, we found a highly increased frequency of chromosome loss. The bulk of increased chromosome loss in ubr1Delta cells is caused by metabolic stabilization of the ESP1-produced SCC1 fragment. This fragment is the first physiological substrate of the N-end rule pathway that is targeted through its N-terminal residue. A number of yeast proteins bear putative cleavage sites for the ESP1 separin, suggesting other physiological substrates and functions of the N-end rule pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anaphase
  • Arginine
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism*
  • Cell Division
  • Chromatids / physiology
  • Chromosomal Proteins, Non-Histone*
  • Chromosome Segregation*
  • Chromosomes, Fungal / physiology*
  • Cysteine Endopeptidases / metabolism
  • Dipeptides / metabolism
  • Endopeptidases*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Half-Life
  • Ligases*
  • Multienzyme Complexes / metabolism
  • Nuclear Proteins
  • Peptide Fragments / metabolism
  • Phosphoproteins
  • Proteasome Endopeptidase Complex
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Separase
  • Ubiquitin-Protein Ligases*
  • Ubiquitins / metabolism


  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Dipeptides
  • Fungal Proteins
  • MCD1 protein, S cerevisiae
  • Multienzyme Complexes
  • Nuclear Proteins
  • Peptide Fragments
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Ubiquitins
  • structural maintenance of chromosome protein 1
  • Arginine
  • UBR1 protein, S cerevisiae
  • Ubiquitin-Protein Ligases
  • Endopeptidases
  • Cysteine Endopeptidases
  • ESP1 protein, S cerevisiae
  • Separase
  • Proteasome Endopeptidase Complex
  • Ligases