The origin recognition complex functions in sister-chromatid cohesion in Saccharomyces cerevisiae.
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.
Shimada
Kenji
K
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
Gasser
Susan M
SM
D000123:Acetyltransferases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002842:Chromatids / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D023902:Chromosome Pairing; D015825:Chromosomes, Fungal / Q000378:metabolism*; D004249:DNA Damage; D004261:DNA Replication; D016193:G1 Phase; D064246:Mad2 Proteins; D008938:Mitosis; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism; D051738:Origin Recognition Complex / Q000172:deficiency / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D051738:Origin Recognition Complex; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1; C577695:MAD2 protein, S cerevisiae; C497215:ORC2 protein, S cerevisiae; C118076:ECO1 protein, S cerevisiae