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Cell. 2007 Jan 12;128(1):85-99.

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

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  • 1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.


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.

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