Document Detail

System-level feedbacks make the anaphase switch irreversible.
MedLine Citation:
PMID:  21617094     Owner:  NLM     Status:  MEDLINE    
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.
Enuo He; Orsolya Kapuy; Raquel A Oliveira; Frank Uhlmann; John J Tyson; Béla Novák
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-26
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-15     Completed Date:  2011-09-29     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10016-21     Citation Subset:  IM    
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MeSH Terms
Anaphase / genetics*
Cell Cycle Proteins / genetics,  metabolism
Chromatids / genetics
Chromosome Segregation / genetics
Cyclin B
Feedback, Physiological*
Mitosis / genetics
Models, Genetic*
Spindle Apparatus / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Cyclin B

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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