Reverse engineering of the Spindle Assembly Checkpoint

Andreas Doncic, Eshel Ben-Jacob, Shmuel Einav, Naama Barkai

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The Spindle Assembly Checkpoint (SAC) is an intracellular mechanism that ensures proper chromosome segregation. By inhibiting Cdc20, a co-factor of the Anaphase Promoting Complex (APC), the checkpoint arrests the cell cycle until all chromosomes are properly attached to the mitotic spindle. Inhibition of Cdc20 is mediated by a conserved network of interacting proteins. The individual functions of these proteins are well characterized, but understanding of their integrated function is still rudimentary. We here describe our attempts to reverse-engineer the SAC network based on gene deletion phenotypes. We begun by formulating a general model of the SAC which enables us to predict the rate of chromosomal missegregation for any putative set of interactions between the SAC proteins. Next the missegregation rates of seven yeast strains are measured in response to the deletion of one or two checkpoint proteins. Finally, we searched for the set of interactions that correctly predicted the observed missegregation rates of all deletion mutants. Remarkably, although based on only seven phenotypes, the consistent network we obtained successfully reproduces many of the known properties of the SAC. Further insights provided by our analysis are discussed.

Original languageEnglish (US)
Article numbere6495
JournalPLoS One
Volume4
Issue number8
DOIs
StatePublished - Aug 4 2009

Fingerprint

M Phase Cell Cycle Checkpoints
Reverse engineering
engineering
Chromosomes
Cell Cycle Checkpoints
proteins
phenotype
Proteins
mitotic spindle apparatus
chromosome segregation
Anaphase-Promoting Complex-Cyclosome
gene deletion
Phenotype
Chromosome Segregation
Spindle Apparatus
engineers
Gene Deletion
Yeast
yeasts
chromosomes

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Doncic, A., Ben-Jacob, E., Einav, S., & Barkai, N. (2009). Reverse engineering of the Spindle Assembly Checkpoint. PLoS One, 4(8), [e6495]. https://doi.org/10.1371/journal.pone.0006495

Reverse engineering of the Spindle Assembly Checkpoint. / Doncic, Andreas; Ben-Jacob, Eshel; Einav, Shmuel; Barkai, Naama.

In: PLoS One, Vol. 4, No. 8, e6495, 04.08.2009.

Research output: Contribution to journalArticle

Doncic, A, Ben-Jacob, E, Einav, S & Barkai, N 2009, 'Reverse engineering of the Spindle Assembly Checkpoint', PLoS One, vol. 4, no. 8, e6495. https://doi.org/10.1371/journal.pone.0006495
Doncic, Andreas ; Ben-Jacob, Eshel ; Einav, Shmuel ; Barkai, Naama. / Reverse engineering of the Spindle Assembly Checkpoint. In: PLoS One. 2009 ; Vol. 4, No. 8.
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