Reverse Engineering of the Spindle Assembly Checkpoint 英文参考文献.docVIP

Reverse Engineering of the Spindle Assembly Checkpoint 英文参考文献.doc

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Reverse Engineering of the Spindle Assembly Checkpoint 英文参考文献

ReverseEngineeringoftheSpindleAssembly Checkpoint AndreasDoncic1,2,EshelBen-Jacob3,ShmuelEinav2,NaamaBarkai1,4* 1DepartmentofMolecularGenetics,WeizmannInstituteofScience,Rehovot,Israel,2DepartmentofBiomedicalEngineering,TheIbyandAladarFleischmanFacultyof Engineering,TelAvivUniversity,RamatAviv,Israel,3SchoolofPhysicsandAstronomy,BeverlyandRaymondSacklerFacultyofExactSciences,TelAvivUniversity,Tel Aviv,Israel,4DepartmentofPhysicsofComplexSystems,WeizmannInstituteofScience,Rehovot,Israel 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 interactingproteins.Theindividualfunctionsoftheseproteinsarewellcharacterized,butunderstandingoftheirintegrated functionisstillrudimentary.Weheredescribeourattemptstoreverse-engineertheSACnetworkbasedongenedeletion phenotypes.WebegunbyformulatingageneralmodeloftheSACwhichenablesustopredicttherateofchromosomal missegregationforanyputativesetofinteractionsbetweentheSACproteins.Nextthemissegregationratesofsevenyeast strains are measured in response to the deletion of one or two checkpoint proteins. Finally, we searched for the set of interactionsthatcorrectlypredictedtheobservedmissegregationratesofalldeletionmutants.Remarkably,althoughbased ononlysevenphenotypes,theconsistentnetworkweobtainedsuccessfullyreproducesmanyoftheknownpropertiesof theSAC.Furtherinsightsprovidedbyouranalysisarediscussed. Citation: Doncic A, Ben-Jacob E, Einav S, Barkai N (2009) Reverse Engineering of the Spindle Assembly Checkpoint. PLoS ONE 4(8): e6495. doi:10.1371/ journal.pone.0006495 Editor:RayaKhanin,UniversityofGlasgow,UnitedKingdom ReceivedFebruary22,2009;AcceptedJuly3,2009;PublishedAugust4,2009 Copyright: ? 2009 Doncic et al. This is an open-access a

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