Reverse engineering of the spindle assembly checkpoint.

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. Inhibiti...

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Autores principales:	Andreas Doncic, Eshel Ben-Jacob, Shmuel Einav, Naama Barkai
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a44fb7ece94e4442926fe0674cd33739
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spelling	oai:doaj.org-article:a44fb7ece94e4442926fe0674cd337392021-11-25T06:21:14ZReverse engineering of the spindle assembly checkpoint.1932-620310.1371/journal.pone.0006495https://doaj.org/article/a44fb7ece94e4442926fe0674cd337392009-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19652707/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Andreas DoncicEshel Ben-JacobShmuel EinavNaama BarkaiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 8, p e6495 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andreas Doncic Eshel Ben-Jacob Shmuel Einav Naama Barkai Reverse engineering of the spindle assembly checkpoint.
description	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.
format	article
author	Andreas Doncic Eshel Ben-Jacob Shmuel Einav Naama Barkai
author_facet	Andreas Doncic Eshel Ben-Jacob Shmuel Einav Naama Barkai
author_sort	Andreas Doncic
title	Reverse engineering of the spindle assembly checkpoint.
title_short	Reverse engineering of the spindle assembly checkpoint.
title_full	Reverse engineering of the spindle assembly checkpoint.
title_fullStr	Reverse engineering of the spindle assembly checkpoint.
title_full_unstemmed	Reverse engineering of the spindle assembly checkpoint.
title_sort	reverse engineering of the spindle assembly checkpoint.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/a44fb7ece94e4442926fe0674cd33739
work_keys_str_mv	AT andreasdoncic reverseengineeringofthespindleassemblycheckpoint AT eshelbenjacob reverseengineeringofthespindleassemblycheckpoint AT shmueleinav reverseengineeringofthespindleassemblycheckpoint AT naamabarkai reverseengineeringofthespindleassemblycheckpoint
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Reverse engineering of the spindle assembly checkpoint.

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