Chromatids (green) fall apart when ORC vanishes (bottom).


One mechanism for holding sister chromatids together during mitosis isn't enough, report Kenji Shimada and Susan Gasser (Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland). They identify a second mechanism that involves the origin recognition complex, which serves earlier in the cell cycle to instigate DNA replication.

The cohesin complex connects sister chromatids until the metaphase-to-anaphase transition. But Shimada and Gasser depleted one of the ORC components from yeast cells and found evidence that it helps out. When production of one ORC component was switched off after replication was complete, the cells stalled in the G2 or M phase. The spindle checkpoint was activated, indicating that chromatid cohesion had gone awry. When the researchers tracked sister chromatid adhesion in cells lacking ORC, they found that the strands were prematurely separating at all three positions they checked. Reinstating the ORC component spurred the chromatids to reunite.

Shimada and Gasser also determined that inserting extra copies of an ARS, an ORC-binding locus, into one yeast chromosome could restore normal sister attachment, even in cells lacking functional cohesin. The researchers conclude that, although ORC can't substitute for cohesin, the two complexes operate independently to strap sister chromatids together. Why cells need two methods to secure sister chromatids is a mystery, says Gasser. But, she adds, ORC's sister act may be a side effect of another of its suspected functions: linking heterochromatin domains.


Shimada, K., and S. Gasser.