COSA-1, a meiotic crossover site associated protein
Abstract/Contents
- Abstract
- The formation of crossovers during meiosis is important both for the reassortment of genetic traits, and for creating a physical connection between homologous chromosomes to ensure faithful segregation. This thesis explores the role of a novel protein, COSA-1 (crossover site associated-1), in forming crossovers in the nematode C. elegans. cosa-1 was isolated in a screen for dead embryos, signaling missegregation of the autosomes, and a high incidence of males, signaling missegregation of the X chromosome. Interestingly, obvious orthologs of COSA-1 are only present in metazoans with the notable exception of Drosophilids. Thus no obvious orthologs of COSA-1 exist in the common model organisms, S. cerevisiae, S. pombe, D. melanogaster, and A. thaliana, making C. elegans one of the few organisms in which COSA-1 could have been isolated and studied. Yet, COSA-1 is conserved into humans suggesting the study of COSA-1 will have implications for human reproduction. Not only does C. elegans cosa-1 play a crucial role in promoting the formation of crossovers, evidenced by the lack of chiasmata in the cosa-1 mutant, GFP::COSA-1 exhibits an interesting localization pattern to presumptive crossover sites. In particular, unlike other crossover promoting proteins MSH-5 and ZHP-3, GFP::COSA-1 does not exhibit an initial broader localization but instead localizes to just 6 foci, 1 focus for the 1 crossover on each of the 6 chromosomes. This localization of GFP::COSA-1 to 6 foci was robust under various conditions. Mathematical modeling of the relationship between irradiation dose and COSA-1 foci revealed a relationship between obligate crossover, the phenomenon in which at least one crossover is formed per chromosome, and crossover interference, the phenomenon in which the formation of a crossover inhibits the formation of other crossovers nearby. In addition, analysis of GFP::COSA-1 foci in mutants that form extra crossovers, in particular rtel-1 and dpy-28, revealed a separation between the number of GFP::COSA-1 foci, 6, and the number of COs made, more than 6, suggesting that interference is still operating on GFP::COSA-1foci. Thus GFP::COSA-1 may serve as a better readout for crossover interference than crossovers per se. The ability to visualize GFP::COSA-1 in live worms holds great potential for elucidating the mechanisms involved in crossover interference, crossover distribution, and crossover designation.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Yokoo, Rayka | |
|---|---|---|
| Associated with | Stanford University, Department of Genetics | |
| Primary advisor | Villeneuve, Anne, 1959- | |
| Thesis advisor | Villeneuve, Anne, 1959- | |
| Thesis advisor | Bejerano, Gill, 1970- | |
| Thesis advisor | Fire, Andrew Zachary | |
| Thesis advisor | Pringle, John | |
| Advisor | Bejerano, Gill, 1970- | |
| Advisor | Fire, Andrew Zachary | |
| Advisor | Pringle, John |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Rayka Yokoo. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Ph. D. Stanford University 2011 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Rayka Yokoo
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...