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The mitotic checkpoint is exquisitely sensitive in that a single unaligned chromosome, 1 of a total of \u223c50, is sufficient to delay progression into anaphase; however, when the last chromosome comes into alignment on the metaphase plate, the mitotic checkpoint is quickly satisfied, and the replicated chromosomes are rapidly partitioned to opposite poles of the dividing cell. The mitotic checkpoint is also curious in the sense that, before metaphase alignment, chromosomes that are not being pulled in opposite directions by the mitotic spindle activate the checkpoint, but during anaphase, these same tensionless chromosomes can no longer activate the checkpoint. These and other puzzles associated with the mitotic checkpoint are addressed by a proposed molecular mechanism, which involves two positive feedback loops that create a bistable response of the checkpoint to chromosomal tension.<\/jats:p>","DOI":"10.1073\/pnas.1102106108","type":"journal-article","created":{"date-parts":[[2011,5,27]],"date-time":"2011-05-27T00:47:17Z","timestamp":1306457237000},"page":"10016-10021","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":57,"title":["System-level feedbacks make the anaphase switch irreversible"],"prefix":"10.1073","volume":"108","author":[{"given":"Enuo","family":"He","sequence":"first","affiliation":[{"name":"Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom;"}]},{"given":"Orsolya","family":"Kapuy","sequence":"additional","affiliation":[{"name":"Oxford Centre for Integrative Systems Biology, Department of 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