Abstract

This proposal is a response to NOT-OD-09-058 Notice of Availability of Recovery Act Funds for Competing Revision Applications. The transmission of genetic material in each cell division requires its accurate duplication and distribution to the daughter cells. The chromosomes are segregated into two equivalent parts by a microtubule-based molecular machine, the mitotic spindle. The parent grant focuses on the assembly and regulation of the mitotic spindle, with emphasis on proteins that bind to the microtubule. These include the gamma-tubulin complex at the centrosome and the Dam1 complex and the Ndc80 complex at the kinetochore. The Dam1 and Ndc80 complexes are required to form strong but dynamic attachments between the chromosomes and the microtubules, but they are not the only components involved. This proposal would fund a new research objective to express and analyze additional kinetochore components to fully reconstitute the microtubule-binding activity of the kinetochore.

Public Health Relevance

Accurate chromosome segregation is required for propagation of all cells. Errors in this process are implicated in oncogenesis, birth defects and cell death. Crucial to proper partitioning of the chromosomes during cell division is the establishment of the mitotic spindle, a microtubule- based molecular machine. The kinetochore is essential for this process.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM040506-20S1
Application #
7807810
Study Section
Special Emphasis Panel (ZRG1-CB-B (95))
Program Officer
Deatherage, James F
Project Start
2009-09-30
Project End
2011-01-31
Budget Start
2009-09-30
Budget End
2011-01-31
Support Year
20
Fiscal Year
2009
Total Cost
$272,551
Indirect Cost

  Institution

Name
University of Washington
Department
Biochemistry
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Helgeson, Luke A; Zelter, Alex; Riffle, Michael et al. (2018) Human Ska complex and Ndc80 complex interact to form a load-bearing assembly that strengthens kinetochore-microtubule attachments. Proc Natl Acad Sci U S A 115:2740-2745
Kim, Jae Ook; Zelter, Alex; Umbreit, Neil T et al. (2017) The Ndc80 complex bridges two Dam1 complex rings. Elife 6:
Kudalkar, Emily M; Deng, Yi; Davis, Trisha N et al. (2016) Coverslip Cleaning and Functionalization for Total Internal Reflection Fluorescence Microscopy. Cold Spring Harb Protoc 2016:pdb.prot085548
Kudalkar, Emily M; Davis, Trisha N; Asbury, Charles L (2016) Single-Molecule Total Internal Reflection Fluorescence Microscopy. Cold Spring Harb Protoc 2016:pdb.top077800
Hsia, Yang; Bale, Jacob B; Gonen, Shane et al. (2016) Design of a hyperstable 60-subunit protein dodecahedron. [corrected]. Nature 535:136-9
Kudalkar, Emily M; Davis, Trisha N; Asbury, Charles L (2016) Preparation of Reactions for Imaging with Total Internal Reflection Fluorescence Microscopy. Cold Spring Harb Protoc 2016:pdb.prot085563
Kollman, Justin M; Greenberg, Charles H; Li, Sam et al. (2015) Ring closure activates yeast ?TuRC for species-specific microtubule nucleation. Nat Struct Mol Biol 22:132-7
Kudalkar, Emily M; Scarborough, Emily A; Umbreit, Neil T et al. (2015) Regulation of outer kinetochore Ndc80 complex-based microtubule attachments by the central kinetochore Mis12/MIND complex. Proc Natl Acad Sci U S A 112:E5583-9
Zelter, Alex; Bonomi, Massimiliano; Kim, Jae ook et al. (2015) The molecular architecture of the Dam1 kinetochore complex is defined by cross-linking based structural modelling. Nat Commun 6:8673
Tien, Jerry F; Umbreit, Neil T; Zelter, Alex et al. (2014) Kinetochore biorientation in Saccharomyces cerevisiae requires a tightly folded conformation of the Ndc80 complex. Genetics 198:1483-93

Showing the most recent 10 out of 58 publications