Abstract

The objective of the experiments proposed in this application are to identify and functionally characterize the structural proteins that comprise the spindle matrix through the following specific aims: l. Using a cell-free mitotic aster assembly system that is highly enriched in the components of the mitotic spindle matrix, the investigator will prepare antibodies that specifically recognize the three major proteins of the mitotic spindle matrix. 2. Using the antibodies prepared in Specific Aim l, the investigator will use immunodepletion and microinjection to determine if each of these proteins is required for the assembly of the mitotic spindle. 3. Using the antibodies prepared in Specific Aim l, he will isolate cDNA clones encoding each of these proteins of the mitotic spindle matrix and determine their primary amino acid sequence.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM051542-04
Application #
6019026
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1996-08-01
Project End
2001-02-28
Budget Start
1999-08-01
Budget End
2001-02-28
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Dartmouth College
Department
Biochemistry
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755

  Publications

Dumitru, Ana Maria G; Rusin, Scott F; Clark, Amber E M et al. (2017) Cyclin A/Cdk1 modulates Plk1 activity in prometaphase to regulate kinetochore-microtubule attachment stability. Elife 6:
Orr, Bernardo; Talje, Lama; Liu, Zhexian et al. (2016) Adaptive Resistance to an Inhibitor of Chromosomal Instability in Human Cancer Cells. Cell Rep 17:1755-1763
Kim, Jung-Sik; He, Xiaoyuan; Orr, Bernardo et al. (2016) Intact Cohesion, Anaphase, and Chromosome Segregation in Human Cells Harboring Tumor-Derived Mutations in STAG2. PLoS Genet 12:e1005865
Godek, Kristina M; Kabeche, Lilian; Compton, Duane A (2015) Regulation of kinetochore-microtubule attachments through homeostatic control during mitosis. Nat Rev Mol Cell Biol 16:57-64
Meppelink, Amanda; Kabeche, Lilian; Vromans, Martijn J M et al. (2015) Shugoshin-1 balances Aurora B kinase activity via PP2A to promote chromosome bi-orientation. Cell Rep 11:508-15
Bakhoum, Samuel F; Silkworth, William T; Nardi, Isaac K et al. (2014) The mitotic origin of chromosomal instability. Curr Biol 24:R148-9
Kleyman, Marianna; Kabeche, Lilian; Compton, Duane A (2014) STAG2 promotes error correction in mitosis by regulating kinetochore-microtubule attachments. J Cell Sci 127:4225-33
Kabeche, Lilian; Compton, Duane A (2013) Cyclin A regulates kinetochore microtubules to promote faithful chromosome segregation. Nature 502:110-3
Hood, Emily A; Kettenbach, Arminja N; Gerber, Scott A et al. (2012) Plk1 regulates the kinesin-13 protein Kif2b to promote faithful chromosome segregation. Mol Biol Cell 23:2264-74
Maia, Ana R R; Garcia, Zaira; Kabeche, Lilian et al. (2012) Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore-microtubule attachments. J Cell Biol 199:285-301

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