System-level feedbacks make the anaphase switch irreversible

Enuo He, Orsolya Kapuy, Raquel A. Oliveira, Frank Uhlmann, John J. Tyson, Béla Novák

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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 languageEnglish
Pages (from-to)10016-10021
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number24
DOIs
Publication statusPublished - Jun 14 2011

Keywords

  • Bistability
  • Cell cycle
  • Irreversible transition
  • Mitotic checkpoint
  • Spindle assembly checkpoint

ASJC Scopus subject areas

  • General

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