Kinetochore protein phosphorylation promotes the correction of erroneous microtubule attachments to ensure faithful chromosome segregation during cell division. Determining how phosphorylation executes error correction requires an understanding of whether kinetochore substrates are completely (i.e. all-or-none) or only fractionally phosphorylated. Using quantitative mass spectrometry (MS), we measured phospho-occupancy on the conserved kinetochore protein Hec1 (NDC80) that directly binds microtubules. None of the positions measured exceeded ~50% phospho-occupancy, and the cumulative phospho-occupancy changed by only ~20% in response to changes in microtubule attachment status. The narrow dynamic range of phospho-occupancy is maintained, in part, by ongoing phosphatase activity. Further, both Cdk1-Cyclin B1 and Aurora kinases phosphorylate Hec1 to enhance error correction in response to different types of microtubule attachment errors. The low inherent phospho-occupancy promotes microtubule attachment to kinetochores while the high sensitivity of kinetochore-microtubule attachments to small changes in phospho-occupancy drives error correction and ensures high mitotic fidelity.
[doi:10.25345/C5F18SJ9Z]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: kinetochore ; phosphorylation ; microtubule ; chromosome segregation ; mitosis ; phospho-occupancy ; Hec1 ; NDC80 ; Cdk1 ; Cyclin B1 ; Aurora
Principal Investigators: (in alphabetical order) |
Scott Gerber, The Geisel School of Medicine at Dartmouth, United States |
Submitting User: | madamo |
Number of Files: | |
Total Size: | |
Spectra: | |
Subscribers: | |
Owner | Reanalyses | |
---|---|---|
Experimental Design | ||
Conditions:
|
||
Biological Replicates:
|
||
Technical Replicates:
|
||
Identification Results | ||
Proteins (Human, Remapped):
|
||
Proteins (Reported):
|
||
Peptides:
|
||
Variant Peptides:
|
||
PSMs:
|
||
Quantification Results | ||
Differential Proteins:
|
||
Quantified Proteins:
|
||
Browse Dataset Files | Browse Results |
FTP Download Link (click to copy):
|