C. elegans DSB-3 reveals conservation and divergence among protein complexes promoting meiotic double-strand breaks
Abstract/Contents
- Abstract
- Meiotic recombination plays dual roles in the evolution and stable inheritance of genomes: recombination promotes genetic diversity by reassorting variants, and it establishes temporary connections between pairs of homologous chromosomes that ensure their future segregation. Meiotic recombination is initiated by generation of double-strand DNA breaks (DSBs) by the conserved topoisomerase-like protein Spo11. Despite strong conservation of Spo11 across kingdoms, auxiliary complexes that interact with Spo11 complexes to promote DSB formation are very poorly conserved. Here, I identify DSB-3 as a DSB promoting protein in C. elegans. Mutants lacking DSB-3 are proficient for homolog pairing and synapsis but fail to form meiotic crossovers. Lack of crossovers in dsb-3 mutants reflects a requirement for DSB-3 in meiotic DSB formation. DSB-3 concentrates in meiotic nuclei with timing similar to DSB-1 and DSB-2 (putative homologs of yeast/mammalian Rec114/REC114), and DSB-1, -2, and -3 are interdependent for this localization. Bioinformatics analysis and interactions among the DSB proteins support the identity of DSB-3 as a homolog of MEI4 in conserved DSB-promoting complexes. This identification is reinforced by colocalization of pairwise combinations of DSB-1, -2, and -3 foci in structured illumination microscopy images of spread nuclei. However, unlike their counterparts in mouse and yeast, DSB-1 can interact directly with SPO-11, and C. elegans DSB protein complexes are not concentrated at meiotic chromosome axes. I suggest that rapid divergence of protein complexes that serve essential, yet auxiliary, roles in meiotic recombination may reflect an immediate impact of changes in such proteins on processes that directly affect reproductive success.
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 | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Hinman, Albert Weston |
|---|---|
| Degree supervisor | Villeneuve, Anne, 1959- |
| Thesis advisor | Villeneuve, Anne, 1959- |
| Thesis advisor | Boettiger, Alistair |
| Thesis advisor | Fire, Andrew Zachary |
| Thesis advisor | Lipsick, Joseph Steven, 1955- |
| Thesis advisor | Stearns, Tim |
| Degree committee member | Boettiger, Alistair |
| Degree committee member | Fire, Andrew Zachary |
| Degree committee member | Lipsick, Joseph Steven, 1955- |
| Degree committee member | Stearns, Tim |
| Associated with | Stanford University, Department of Genetics |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Albert Weston Hinman. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2021 by Albert Weston Hinman
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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