The long-term objectives of these studies are to obtain information regarding the regulation of chromosome distribution in higher organisms. The goal is to identify and characterize the forces required for chromosome movement in dividing cells, and determine their roles in chromosome distribution. This proposal concerns nonclaret disjunctional+ (ncd+). Its mutant phenotype of frequent nondisjunction and loss of chromosomes implicates ncd+ in the process of meiotic chromosome segregation in Drosophila females. The predicted ncd+ protein is strikingly similar to the microtubule motor molecule, kinesin. The proposed studies are designed to test two hypotheses. The first is that ncd+ is a motor molecule that acts in oocytes to mediate chromosome movements needed for proper distribution of chromosomes in meiosis. The second hypothesis is that proteins similar to ncd+ are needed to perform a similar role in spermatocytes and in mitosis.
Specific aims are the following: 1.The role of ncd+ in chromosome distribution will be determined by examining its motility properties, cytological location, and the time of action and effect of mutants on chromosome distribution. A genetic screen will be carried out to identify proteins that interact with ncd+. 2.Genes that encode candidates for the ncd+-like proteins that are predicted to act in spermatocytes and in mitotic cells will be identified, isolated and characterized. Male-specific and mitotic homologues will be compared with ncd+ to identify regions of similarity, which may be important functionally, and regions that differ, which may indicate differences in chromosome segregation in meiosis and mitosis. Results of the proposed studies will lead to information regarding the role of ncd+ in chromosome distribution in oocytes, and the identification and isolation of genes that encode ncd+-like proteins that function in spermatocytes and in mitotically dividing cells . This information will contribute to our understanding of the molecular forces needed for proper chromosome distribution in dividing cells. Defects in chromosome distribution have harmful consequences for the organism including aneuploidy, infertility and lethality.
| Kull, F Jon; Endow, Sharyn A (2013) Force generation by kinesin and myosin cytoskeletal motor proteins. J Cell Sci 126:9-19 |
| Endow, Sharyn A; Nizami, Zehra F; Gerbi, Susan A (2013) A remarkable career in science-Joseph G. Gall. Chromosome Res 21:339-43 |
| Liu, Hong-Lei; Hallen, Mark A; Endow, Sharyn A (2012) Altered nucleotide-microtubule coupling and increased mechanical output by a kinesin mutant. PLoS One 7:e47148 |
| Liu, Hong-Lei; Pemble 4th, Charles W; Endow, Sharyn A (2012) Neck-motor interactions trigger rotation of the kinesin stalk. Sci Rep 2:236 |
| Hallen, Mark A; Liang, Zhang-Yi; Endow, Sharyn A (2011) Two-state displacement by the kinesin-14 Ncd stalk. Biophys Chem 154:56-65 |
| Endow, Sharyn A; Hallen, Mark A (2011) Anastral spindle assembly and ýý-tubulin in Drosophila oocytes. BMC Cell Biol 12:1 |
| Endow, Sharyn A; Kull, F Jon; Liu, Honglei (2010) Kinesins at a glance. J Cell Sci 123:3420-4 |
| Heuston, Elisabeth; Bronner, C Eric; Kull, F Jon et al. (2010) A kinesin motor in a force-producing conformation. BMC Struct Biol 10:19 |
| Hallen, Mark A; Endow, Sharyn A (2009) Anastral spindle assembly: a mathematical model. Biophys J 97:2191-201 |
| Liu, Honglei; Endow, Sharyn A (2009) Spindle function in yeast: a human motor to the rescue. Cell Cycle 8:3453-4 |
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