Regulation and coordination of homologous pairing and synapsis during caenorhabditis elegans meiosis
Abstract/Contents
- Abstract
- For successful segregation of chromosomes during meiosis, chromosomes have to recognize and align with their correct homologous partners, and then stabilize the homologous alignment with assembly of a proteinaceous structure, called the synaptonemal complex (SC), between them. SC assembly is highly processive and cooperative, yet the SC structure does not distinguish between homologous and nonhomologous associations. Thus SC assembly has to be tightly regulated and coordinated with homologous pairing to ensure that the SC is stabilizing productive homologous associations. Moreover, homologous pairing is accompanied by dramatic chromosome movement and nuclear reorganization of chromosomes into a clustered configuration during C. elegans early meiotic prophase. Subsequently, the clustered chromosomes are redispersed into aligned homologs upon SC assembly. The exact mechanisms involved in regulation and coordination of homologous pairing and synapsis are poorly understood, and this thesis was aimed at gaining a better understanding of the coordination of these two inter-related meiotic events. We identified HAL-2 as a major player in this coordination. We demonstrated that HAL-2 promotes homologous pairing mainly by preventing detrimental effects of SC precursors (SYP proteins). Homologous pairing is not established in hal-2 mutants, and several markers indicative of pairing center-mediated chromosome movement are also absent in hal-2 mutants. Pairing centers (PCs) are cis-acting chromosomal sites that mediate chromosome movement by connecting chromosomes to cytoplasmic microtubules via the conserved SUN-1/ZYG-12 nuclear envelope-spanning complexes. hal-2 mutants also exhibit defective SC assembly, with SYP proteins being loaded inappropriately along single unpaired chromosomes in hal-2 mutants. Moreover markers of PC-mediated chromosome movement and function are coordinately restored in hal-2 mutants by the removal of SYP proteins. Combined with other data, these findings indicate that SYP proteins can inhibit homologous pairing and that HAL-2 promotes pairing largely by antagonizing this inhibition, thus allowing activation and regulation of PC function. Given that HAL-2 concentrates in the nucleoplasm of meiotic germ cells and colocalizes with SYP proteins in nuclear aggregates when SC assembly is prevented, we propose that HAL-2 functions to shepherd SYP proteins prior to licensing of SC assembly, preventing SC precursors from interacting inappropriately with chromosomes and allowing them to accumulate sufficiently for rapid cooperative assembly upon homology verification. In this thesis, we also identified and characterized me16, a hypomorphic allele of scc-3. SCC-3 is a conserved component of the cohesin complex, and the scc-3(me16) mutant was demonstrated to be a partial loss of function mutation by comparative analyses with a null mutant, scc-3(ku263). Besides reduced chromosomal localization of cohesin, scc-3(me16) mutants also display an extended region of clustered chromosomes, incomplete SC assembly and defective recombination. Further, analyses of nuclear aggregates that form in the scc-3(ku263) null mutants led to the findings that components of the lateral elements, including cohesin, colocalize into these nuclear aggregates and that this localization is not dependent on REC-8.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2012 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Zhang, Weibin |
|---|---|
| Associated with | Stanford University, Department of Genetics |
| Primary advisor | Villeneuve, Anne, 1959- |
| Thesis advisor | Villeneuve, Anne, 1959- |
| Thesis advisor | Fire, Andrew Zachary |
| Thesis advisor | Pringle, John |
| Thesis advisor | Stearns, Tim |
| Advisor | Fire, Andrew Zachary |
| Advisor | Pringle, John |
| Advisor | Stearns, Tim |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Weibin Zhang. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2012. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2012 by Weibin Zhang
- License
- This work is licensed under a Creative Commons Attribution Non Commercial No Derivatives 3.0 Unported license (CC BY-NC-ND).
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