COSA-1–SLX-4 interaction directly links crossover designation with Holliday junction resolution
Crossover (CO) formation between homologous chromosomes is essential for genetic diversity and accurate meiotic chromosome segregation. This process involves two key steps: the designation of a subset of meiotic double-strand breaks to CO-designated sites and subsequent CO resolution by Holliday junction (HJ) resolvase. However, how these steps are functionally coupled remains elusive. Here, we showed that COSA-1, essential for CO designation, directly interacts with the SLX-4 scaffold protein, which organizes the SLX-1, XPF-1, and MUS-81 HJ resolvases. Disrupting this interaction results in persistent unrepaired recombination intermediates and defective CO formation. Notably, these defects can be largely rescued by the artificial tethering of SLX-4 to the CO designation proteins. We further demonstrate that COSA-1 promotes assembly of the SLX-4 resolvase complex and provide evidence that this mechanism coupling CO designation with resolution is evolutionarily conserved. Together, our findings support a model in which CO designation proteins ensure accurate CO formation by directly recruiting the resolution machinery.
Authors
- Yi Yang (ORCID: https://orcid.org/0000-0002-4091-8532)
- Anton Gartner (ORCID: https://orcid.org/0000-0003-4639-9902)
- Meiyu Zhang (ORCID: https://orcid.org/0000-0003-4634-6800)
- Xuezhen Wu (ORCID: https://orcid.org/0000-0001-6310-9124)
- Ye Hong (ORCID: https://orcid.org/0009-0005-7980-6414)
- Yuchen Wang (ORCID: https://orcid.org/0000-0002-6710-6710)
- Hu Zhang (ORCID: https://orcid.org/0000-0002-7447-8360)
- Wencong Nan
- Guoteng Liu
- Tongxin Xiao
- Zongyu Guo
Institutions
- Shandong University (CN)
- Shandong Tumor Hospital (CN)
- Institute for Basic Science (KR)
- Suzhou Research Institute (CN)
- Shandong First Medical University (CN)
- Ulsan National Institute of Science and Technology (KR)
Publication Details
- Journal
- Science Advances
- Published
- 2026-04-24
- DOI
- https://doi.org/10.1126/sciadv.adx9148
- Primary Topic
- DNA Repair Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Shandong University
- National Natural Science Foundation of China
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province
- Natural Science Foundation of Shandong Province