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The mitotic checkpoint prevents a eukaryotic cell from commencing to separate its replicated genome into two daughter cells (anaphase) until all of its chromosomes are properly aligned on the metaphase plate, with the two copies of each chromosome attached to opposite poles of the mitotic spindle. The mitotic checkpoint is exquisitely sensitive in that a single unaligned chromosome, 1 of a total of ~50, 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.

Original publication

DOI

10.1073/pnas.1102106108

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

14/06/2011

Volume

108

Pages

10016 - 10021

Keywords

Algorithms, Anaphase, Animals, Cell Cycle Proteins, Chromatids, Chromosome Segregation, Cyclin B, Feedback, Physiological, Humans, Mitosis, Models, Genetic, Spindle Apparatus