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No stretch for spindle assembly checkpoint

Kinetochores (red) attach to the spindle (green), whereas chromatin (blue) is largely excluded.

Dividing cells aren't quite as obsessed with quality control as previously thought, according to results from O'Connell and colleagues.

The spindle assembly checkpoint assures that chromosomes segregate properly during mitosis. This checkpoint has been thought to monitor two separate events: the attachment of kinetochores to spindle fibers, and the stretch force across the centromere as paired sister chromatid kinetochores start to pull apart. But whether detection of stretch is required to satisfy the checkpoint has never been conclusively demonstrated. To test this, the authors treated cells with hydroxyurea to inhibit replication, creating cells that undergo mitosis with unreplicated genomes (MUG). Such cells contain normal centrosomes and form bipolar spindles, but each kinetochore is unreplicated; thus, inner centromere stretch is not possible.

MUG cells weren't normal in every respect—their kinetochores were separated from the bulk of chromatin, unattached chromatin was largely excluded from the spindle apparatus, and the duration of mitosis was more variable and longer on average than in normal cells. Nonetheless, a normal bipolar spindle formed, and kinetochores attached to spindle microtubules, aligned at the equator, and moved to the poles at anaphase—even without centromeric stretch. In contrast, when the team induced microtubule depolymerization, mitosis was arrested, indicating MUG cells possess a spindle assembly checkpoint that relies on kinetochores attaching to intact spindle fibers.

These results don't necessarily imply that stretch is unimportant or unmonitored, says lead investigator Christopher O'Connell, only that its absence cannot halt anaphase. If stretch is monitored, he says, the correction mechanism is likely to be so rapid that delaying mitosis is unnecessary to resolve the problem.

O'Connell, C.B., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200801038.[Abstract/Free Full Text]

Richard Robinson

rrobinson{at}nasw.org

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This Article Full Text (PDF, 906K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Robinson, R. Search for Related Content PubMed Articles by Robinson, R. Social Bookmarking                            What's this?