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Science 4 August 2006: Vol. 313. no. 5787, p. 588 DOI: 10.1126/science.313.5787.588o
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This Week in Science
The spindle checkpoint is a key mechanism that assures accurate distribution of the chromosomes during cell division, by delaying completion of mitosis until kinetochores of the chromosomes are attached to spindle microtubules and until tension is being applied to pull the sister kinetochores toward opposite spindle poles. Why then, once anaphase begins and the sister chromatids begin to separate, is the checkpoint not reactivated? Palframan et al. (p. 680, published online 12 July; see the Perspective by Hoyt) describe a feedback loop of mutual inhibition between the APC (anaphase-promoting complex, a ubiqitin E3 ligase complex that targets proteins for degradation) and Mps1 (a protein kinase that is part of the checkpoint signaling pathway). Once the checkpoint conditions are satisfied and anaphase begins, the inhibition of APC by Mps1 appears to dip below a critical threshold. At this point, the APC apparently switches to an "on" state in which anaphase is promoted and Mps1 (which is itself a target of the APC) is degraded and can thus no longer activate the checkpoint.
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Science. ISSN 0036-8075 (print), 1095-9203 (online)