Homologous recombination during C. elegans meiosis : regulation of chromosome organization and DNA repair machinery
Abstract/Contents
- Abstract
- Engagement of the homologous chromosome is an essential aspect of meiosis, the conserved, developmental program which allows diploid organisms to create haploid gametes. For their faithful segregation in the first meiotic division, homologs must identify each other and become stably connected. In my thesis work, I have sought to understand the cellular mechanisms that promote homolog pairing and connection in C. elegans meiotic prophase cells. First, in chapter 2, I attempt to shed light on the long-enigmatic question of how homolog partner recognition is achieved in C. elegans. Homologs are paired in C. elegans through cis-acting chromosomal regions called pairing centers (PCs), but how PCs function in homolog partner recognition is unclear. To better understand the mechanism of action of PCs, I sought to characterize their 3D physical structure by adapting the Optical Reconstruction of Chromatin Architecture (ORCA) method to C. elegans germ cells. Because of technical challenges encountered during analysis of ORCA data, I did not obtain new biological insights about PC function. However, my work on ORCA adaptation contributed to a different project focused on meiotic chromosome organization by the chromosome axis proteins. The findings of this project are detailed in chapter 3. The primary contribution of my thesis work is described in chapter 4, which is broadly focused on the cellular mechanisms that promote homolog connection during meiotic prophase. Homologs become physically connected during meiosis by a crossover, which is formed through repair of programmed DNA double-strand breaks (DSBs). Once programmed DSBs have been induced, recombinase proteins conduct critical early steps of the DSB repair (DSBR) pathway: the repair template search and strand exchange reactions. In this chapter, I investigate how C. elegans recombinase RAD-51 is regulated during meiotic DSBR by partner proteins in the RAD-54 family, showing that two RAD-54 family paralogs, RAD-54.L and RAD-54.B, make distinct contributions to the dynamics of RAD-51 association with DNA and DSBR progression. We propose that this division of labor between the two RAD-54 family paralogs enables the meiotic DSBR machinery to ramp up their capacity for efficient DSB processing, while also counteracting the potentially deleterious effects of hyperactivation of the DSBR machinery.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Yamaya, Kei |
|---|---|
| Degree supervisor | Villeneuve, Anne, 1959- |
| Thesis advisor | Villeneuve, Anne, 1959- |
| Thesis advisor | Boettiger, Alistair |
| Thesis advisor | Fire, Andrew Zachary |
| Thesis advisor | Goins, Lauren (Lauren Monica) |
| Degree committee member | Boettiger, Alistair |
| Degree committee member | Fire, Andrew Zachary |
| Degree committee member | Goins, Lauren (Lauren Monica) |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Department of Developmental Biology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Kei Yamaya. |
|---|---|
| Note | Submitted to the Department of Developmental Biology. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/cc394hm1894 |
Access conditions
- Copyright
- © 2023 by Kei Yamaya
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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