First
recognized over one hundred years ago as a key organizer of cellular
structure, the centrosome remains one of the great mysteries of modern
cell biology. From the molecular composition, to the structural
organization, to the intriguing process of duplication, our
understanding is rudimentary. Cells start the cell cycle with a single
centrosome which duplicates only once each cycle. The two centrosomes
organize the microtubules that make up the mitotic spindle and thereby
play a crucial role in ensuring that each daughter cell receives
exactly one copy of each chromosome. In cancer cells, this process goes
awry resulting in cells with multiple centrosomes as well as abnormal
mitotic spindles.
The
functional equivalent of the centrosome in the unicellular eukaryote
Saccharomyces cerevisiae is a cylindrical multilayered structure called
the spindle pole body (SPB). As the name suggests, the two SPBs form
the poles of the mitotic spindle. They also organize the cytoplasmic
microtubules that reach to the cortex of the cell and position the
nucleus. Although SPBs do not resemble centrosomes on the
ultrastructural level, the majority of known SPB components have
homologues found in the animal cell centrosome. The centrosome and the
SPB perform similar functions and contain similar components. Thus, a
detailed understanding of the regulation, structure and assembly of the
yeast SPB will yield important insights into animal cell centrosomes.
We are exploiting our ability to manipulate yeast genes at will to
define the properties of this central and essential organizer.
Selected
Publications
Flory,
M. R., M. Morphew, J. D. Joseph, A. R. Means, and T. N. Davis (2002)
Pcp1p, an Spc110p-related calmodulin target at the centrosome of the
fission yeast Schizosaccharomyces pombe. Cell Growth Differ. 13:47-58.
Vinh,
D. B. N., J. W. Kern, W. Hancock, J. Howard and T. N. Davis (2002)
Reconstitution and characterization of the budding yeast gamma-tubulin
complex. Mol. Biol. Cell 13:1144-1157.
Measday,
V. D. W. Hailey, I Pot, S. A. Givan, K M. Hyland, G. Cagney, S. Fields,
T. N. Davis, and P. Hieter (2002) Ctf3p, the Mis6 budding yeast
homolog, interacts with Mcm22p and Mcm16p at the yeast outer
kinetochore. Genes Dev. 16:101-113.
Pot,
I., V. Measday, B. Snydsman, G. Cagney, S. Fields, T. N. Davis, E. G.
D. Muller, and P. Hieter (2003) Chl4p and Iml3p are two new members of
the budding yeast outer kinetochore. Mol. Biol. Cell 14:460-476.
Flory,
M. R. and T. N. Davis. (2003) The centrosomal proteins pericentrin and
kendrin are encoded by alternatively spliced products of one gene.
Genomics 82:401-405
Yoder,
T J., C. G. Pearson, K. Bloom and T. N. Davis (2003) The Saccharomyces
cerevisiae spindle pole body is a dynamic structure. Mol. Biol. Cell
14:3494-3505.
Hazbun
T. R., L. Malmström, S. Anderson, B. J. Graczyk, B. Fox, M.
Riffle, B.
A. Sundin, J. D. Aranda, W. H. McDonald, C. H. Chun, B. E. Snydsman, P.
Bradley, E. G. D. Muller, S. Fields, D. Baker, J. R. Yates, 3rd, and T.
N. Davis (2003) Assigning function to yeast proteins by integration of
technologies. Mol. Cell 12:1353-1365.
Sundin,
B. A., C.-H. Chiu, M. Riffle, T. N. Davis, and E. G. D. Muller (2004)
Localization of proteins that are coordinately expressed with Cln2
during the cell cycle. Yeast 21:793-800.
Yoder,
T. J., M. A. McElwain, S. E. Francis, J. Bagley, E. G. D. Muller, B.
Pak, E. O'Toole, M. Winey, T. N. Davis, (2004) Analysis of a spindle
pole body mutant reveals defects in bi-orientation and illuminates
spindle forces. Mol Biol Cell 16:141-152.
Riffle,
M., L. Malmstrom, and T. N. Davis. (2005) The Yeast Resource Center
public data repository. Nucleic Acids Res 33 (Database issue):D378-382.
Box 357350 