The origin recognition complex functions in sister-chromatid cohesion in Saccharomyces cerevisiae

Cell. 2007 Jan 12;128(1):85-99. doi: 10.1016/j.cell.2006.11.045.


High-fidelity chromosomal segregation requires the properly timed establishment of sister-chromatid cohesion mediated by the Cohesin complex, and its resolution at the metaphase-to-anaphase transition. We have examined cell-cycle progression in a yeast strain from which the origin recognition complex protein Orc2 was depleted after the assembly of prereplication complexes. We find that Orc2 depletion causes a delay in progression through mitosis, reflecting activation of both the DNA-damage and Mad2-spindle checkpoints. Surprisingly, sister-chromatid cohesion is impaired in Orc2-depleted cells, although Cohesin subunits are properly associated with chromatin. Reexpression of Orc2 in late G2/M phase restores chromatid cohesion. Finally, the targeting of Orc2 to a specific chromosomal locus suppresses premature sister-chromatid separation locally in a temperature-sensitive cohesin mutant. We conclude that ORC mediates sister-chromatid interaction on a pathway that is additive with Cohesin-mediated pairing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / metabolism
  • Cell Cycle Proteins / metabolism
  • Chromatids / metabolism*
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Pairing*
  • Chromosomes, Fungal / metabolism*
  • DNA Damage
  • DNA Replication
  • G1 Phase
  • Mad2 Proteins
  • Mitosis
  • Models, Biological
  • Nuclear Proteins / metabolism
  • Origin Recognition Complex / deficiency
  • Origin Recognition Complex / metabolism*
  • Protein Binding
  • Protein Transport
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Spindle Apparatus / metabolism


  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • MAD2 protein, S cerevisiae
  • Mad2 Proteins
  • Nuclear Proteins
  • ORC2 protein, S cerevisiae
  • Origin Recognition Complex
  • Saccharomyces cerevisiae Proteins
  • cohesins
  • structural maintenance of chromosome protein 1
  • Acetyltransferases
  • ECO1 protein, S cerevisiae