The conserved ATPase PCH-2 controls the number and distribution of crossovers by antagonizing their formation in Caenorhabditis elegans
Meiotic crossover recombination is essential for both accurate chromosome segregation and the generation of new haplotypes for natural selection to act upon. This requirement is known as crossover assurance and is one example of crossover control. While the conserved role of the ATPase, PCH-2, durin...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2025-02-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/102409 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850085534937907200 |
|---|---|
| author | Bhumil Patel Maryke Grobler Alberto Herrera Elias Logari Valery Ortiz Needhi Bhalla |
| author_facet | Bhumil Patel Maryke Grobler Alberto Herrera Elias Logari Valery Ortiz Needhi Bhalla |
| author_sort | Bhumil Patel |
| collection | DOAJ |
| description | Meiotic crossover recombination is essential for both accurate chromosome segregation and the generation of new haplotypes for natural selection to act upon. This requirement is known as crossover assurance and is one example of crossover control. While the conserved role of the ATPase, PCH-2, during meiotic prophase has been enigmatic, a universal phenotype when pch-2 or its orthologs are mutated is a change in the number and distribution of meiotic crossovers. Here, we show that PCH-2 controls the number and distribution of crossovers by antagonizing their formation. This antagonism produces different effects at different stages of meiotic prophase: early in meiotic prophase, PCH-2 prevents double-strand breaks from becoming crossover-eligible intermediates, limiting crossover formation at sites of initial double-strand break formation and homolog interactions. Later in meiotic prophase, PCH-2 winnows the number of crossover-eligible intermediates, contributing to the designation of crossovers and ultimately, crossover assurance. We also demonstrate that PCH-2 accomplishes this regulation through the meiotic HORMAD, HIM-3. Our data strongly support a model in which PCH-2’s conserved role is to remodel meiotic HORMADs throughout meiotic prophase to destabilize crossover-eligible precursors and coordinate meiotic recombination with synapsis, ensuring the progressive implementation of meiotic recombination and explaining its function in the pachytene checkpoint and crossover control. |
| format | Article |
| id | doaj-art-da00e5d7e99743c3aae1bdd577b11bba |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-da00e5d7e99743c3aae1bdd577b11bba2025-08-20T02:43:42ZengeLife Sciences Publications LtdeLife2050-084X2025-02-011310.7554/eLife.102409The conserved ATPase PCH-2 controls the number and distribution of crossovers by antagonizing their formation in Caenorhabditis elegansBhumil Patel0Maryke Grobler1Alberto Herrera2Elias Logari3Valery Ortiz4Needhi Bhalla5https://orcid.org/0000-0002-6859-0073Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, United StatesDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, United StatesDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, United StatesDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, United StatesDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, United StatesDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, United StatesMeiotic crossover recombination is essential for both accurate chromosome segregation and the generation of new haplotypes for natural selection to act upon. This requirement is known as crossover assurance and is one example of crossover control. While the conserved role of the ATPase, PCH-2, during meiotic prophase has been enigmatic, a universal phenotype when pch-2 or its orthologs are mutated is a change in the number and distribution of meiotic crossovers. Here, we show that PCH-2 controls the number and distribution of crossovers by antagonizing their formation. This antagonism produces different effects at different stages of meiotic prophase: early in meiotic prophase, PCH-2 prevents double-strand breaks from becoming crossover-eligible intermediates, limiting crossover formation at sites of initial double-strand break formation and homolog interactions. Later in meiotic prophase, PCH-2 winnows the number of crossover-eligible intermediates, contributing to the designation of crossovers and ultimately, crossover assurance. We also demonstrate that PCH-2 accomplishes this regulation through the meiotic HORMAD, HIM-3. Our data strongly support a model in which PCH-2’s conserved role is to remodel meiotic HORMADs throughout meiotic prophase to destabilize crossover-eligible precursors and coordinate meiotic recombination with synapsis, ensuring the progressive implementation of meiotic recombination and explaining its function in the pachytene checkpoint and crossover control.https://elifesciences.org/articles/102409meiosisrecombinationcrossoversynaptonemal complexsynapsischeckpoint |
| spellingShingle | Bhumil Patel Maryke Grobler Alberto Herrera Elias Logari Valery Ortiz Needhi Bhalla The conserved ATPase PCH-2 controls the number and distribution of crossovers by antagonizing their formation in Caenorhabditis elegans eLife meiosis recombination crossover synaptonemal complex synapsis checkpoint |
| title | The conserved ATPase PCH-2 controls the number and distribution of crossovers by antagonizing their formation in Caenorhabditis elegans |
| title_full | The conserved ATPase PCH-2 controls the number and distribution of crossovers by antagonizing their formation in Caenorhabditis elegans |
| title_fullStr | The conserved ATPase PCH-2 controls the number and distribution of crossovers by antagonizing their formation in Caenorhabditis elegans |
| title_full_unstemmed | The conserved ATPase PCH-2 controls the number and distribution of crossovers by antagonizing their formation in Caenorhabditis elegans |
| title_short | The conserved ATPase PCH-2 controls the number and distribution of crossovers by antagonizing their formation in Caenorhabditis elegans |
| title_sort | conserved atpase pch 2 controls the number and distribution of crossovers by antagonizing their formation in caenorhabditis elegans |
| topic | meiosis recombination crossover synaptonemal complex synapsis checkpoint |
| url | https://elifesciences.org/articles/102409 |
| work_keys_str_mv | AT bhumilpatel theconservedatpasepch2controlsthenumberanddistributionofcrossoversbyantagonizingtheirformationincaenorhabditiselegans AT marykegrobler theconservedatpasepch2controlsthenumberanddistributionofcrossoversbyantagonizingtheirformationincaenorhabditiselegans AT albertoherrera theconservedatpasepch2controlsthenumberanddistributionofcrossoversbyantagonizingtheirformationincaenorhabditiselegans AT eliaslogari theconservedatpasepch2controlsthenumberanddistributionofcrossoversbyantagonizingtheirformationincaenorhabditiselegans AT valeryortiz theconservedatpasepch2controlsthenumberanddistributionofcrossoversbyantagonizingtheirformationincaenorhabditiselegans AT needhibhalla theconservedatpasepch2controlsthenumberanddistributionofcrossoversbyantagonizingtheirformationincaenorhabditiselegans AT bhumilpatel conservedatpasepch2controlsthenumberanddistributionofcrossoversbyantagonizingtheirformationincaenorhabditiselegans AT marykegrobler conservedatpasepch2controlsthenumberanddistributionofcrossoversbyantagonizingtheirformationincaenorhabditiselegans AT albertoherrera conservedatpasepch2controlsthenumberanddistributionofcrossoversbyantagonizingtheirformationincaenorhabditiselegans AT eliaslogari conservedatpasepch2controlsthenumberanddistributionofcrossoversbyantagonizingtheirformationincaenorhabditiselegans AT valeryortiz conservedatpasepch2controlsthenumberanddistributionofcrossoversbyantagonizingtheirformationincaenorhabditiselegans AT needhibhalla conservedatpasepch2controlsthenumberanddistributionofcrossoversbyantagonizingtheirformationincaenorhabditiselegans |