In order for sister chromosomes to be faithfully segregated to opposing daughter cells during cell division, each chromosome must possess a single centromere. The lack of a centromere or the creation of dicentric chromosomes (those possessing two centromeres) leads to chromosomal breakage and missegregation of chromosomes during mitosis. In turn, aberrant chromosome segregation may give rise to developmental abnormalities and neoplastic disease. Furthermore, a better understanding of the components of the human chromosome that govern transmission of genetic information may be important in the development of novel gene therapies.
Specific Aim 1 : By developing a transgenic mouse containing a conditional disruption of the endogenous mouse CENP-A gene, these studies seek to determine whether CENP-A protein is required for the establishment and maintenance of the mammalian centromere.
Specific Aim 2 : Furthermore, using a yeast two-hybrid screen, this study endeavors to identify proteins that interact with CENP-A that may be involved in centromere specification and kinetochore assembly.
Specific Aim3 : Finally, the studies proposed here are designed to determine whether CENP-A itself is sufficient to recruit centromere components and ultimately specify the centromere.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM067401-01
Application #
6584108
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Tompkins, Laurie
Project Start
2003-03-01
Project End
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
1
Fiscal Year
2003
Total Cost
$41,608
Indirect Cost
Name
Ludwig Institute for Cancer Research
Department
Type
DUNS #
627922248
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Barnhart-Dailey, Meghan C; Foltz, Daniel R (2014) Centromere licensing: Mis18 is required to Polo-ver. Curr Biol 24:R808-10
Stellfox, Madison E; Bailey, Aaron O; Foltz, Daniel R (2013) Putting CENP-A in its place. Cell Mol Life Sci 70:387-406
Foltz, Daniel R; Jansen, Lars E T; Bailey, Aaron O et al. (2009) Centromere-specific assembly of CENP-a nucleosomes is mediated by HJURP. Cell 137:472-84