High-fidelity chromosome segregation requires maintaining chromosomes on the metaphase plate until anaphase. The mechanisms by which this occurs are poorly understood. In meiosis, chromosomes that do not crossover are particularly prone to missegregation at the first division. Failure to properly segregate non-crossover, or achiasmate chromosomes leads to many human diseases, including Down syndrome. In Drosophila, a conserved chromokinesin-like protein called Nod is essential to faithfully segregate achiasmate chromosomes. Nod functions in the polar ejection force that maintains chromosomes at the metaphase plate until anaphase. In addition to its role in maintaining chromosomes on the metaphase plate, our lab has recently identified a novel role for Nod in chromosome congression. It is currently unknown whether these functions are separable. The proposed research will directly test this by investigating which domains of Nod are required for Nod's two functions. In addition, this proposal aims to identify key Nod regulators and to understand the mechanism of Nod regulation. To identify genes that regulate Nod function, two complementary approaches will be used: genetics and proteomics. Finally, this proposal will investigate the mechanism of Nod downregulation by asking the question: does Nod relocalize or is Nod degraded at the metaphase to anaphase I transition? Investigating the mechanisms by which chromosomes are properly transmitted from parent to child are essential to understand what goes awry in diseases that result from chromosome abnormalities, such as Down syndrome. This proposal will advance our knowledge of a gene that is required to prevent such errors. In the long-term, this research may lead to fewer children born with diseases due to having an abnormal number of chromosomes.
| Cochran, Jared C; Sindelar, Charles V; Mulko, Natasha K et al. (2009) ATPase cycle of the nonmotile kinesin NOD allows microtubule end tracking and drives chromosome movement. Cell 136:110-22 |
| Hughes, Stacie E; Gilliland, William D; Cotitta, Jeffrey L et al. (2009) Heterochromatic threads connect oscillating chromosomes during prometaphase I in Drosophila oocytes. PLoS Genet 5:e1000348 |
