Roles for the Conserved Spc105pKre28p Complex in Kinetochore-Microtubule Binding and the Spindle Assembly Checkpoint 英文参考文献.docVIP
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Roles for the Conserved Spc105pKre28p Complex in Kinetochore-Microtubule Binding and the Spindle Assembly Checkpoint 英文参考文献
RolesfortheConservedSpc105p/Kre28pComplexin
Kinetochore-MicrotubuleBindingandtheSpindle
AssemblyCheckpoint
CinziaPagliuca1.,VijiM.Draviam2,3,4.,EugenioMarco2,3,PeterK.Sorger2,3,PeterDeWulf1,3
*
1Department of Experimental Oncology, European Institute of Oncology, Milan, Italy, 2Biological Engineering Division, Massachusetts Institute of Technology,
Cambridge, Massachusetts, United States of America, 3Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America,
4DepartmentofGenetics,UniversityofCambridge,Cambridge,UnitedKingdom
Abstract
Background: Kinetochores attach sister chromatids to microtubules of the mitotic spindle and orchestrate chromosome
disjunction at anaphase. Although S. cerevisiae has the simplest known kinetochores, they nonetheless contain ,70
subunitsthatassembleoncentromericDNAinahierarchicalmanner.DevelopinganaccuratepictureoftheDNA-binding,
linkerandmicrotubule-bindinglayersofkinetochores,includingthefunctionsofindividualproteinsintheselayers,isakey
challenge in the field of yeast chromosome segregation. Moreover, comparison of orthologous proteins in yeast and
humans promises to extend insight obtained from the study of simple fungal kinetochores to complex animal cell
kinetochores.
PrincipalFindings:WeshowthatS.cerevisiaeSpc105pformsaheterotrimericcomplexwithKre28p,thelikelyorthologueof
the metazoan kinetochore protein Zwint-1. Through systematic analysis of interdependencies among kinetochore
complexes,focusedonSpc105p/Kre28p,wedevelopacomprehensivepictureoftheassemblyhierarchyofbuddingyeast
kinetochores.WefindSpc105p/Kre28ptocomprisethethirdlinkercomplexthat,alongwiththeNdc80andMINDlinker
complexes,isresponsibleforbridgingbetweencentromericheterochromatinandkinetochoreMAPsandmotors.Likethe
Ndc80 complex, Spc105p/Kre28p is also essential for kinetochore binding by components of the spindle assembly
checkpoint.Moreover,thesefunctionsareconservedinhumancells.
Conclusions/Significance:Spc105p/Kre28pi
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