COSA-1–SLX-4 interaction directly links crossover designation with Holliday junction resolution

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Authors: Guoteng Liu, Yi Yang, Wencong Nan, Tongxin Xiao, Zongyu Guo, Meiyu Zhang, Yuchen Wang, Xuezhen Wu, Anton Gartner, Hu Zhang, Ye Hong
Cited by: 1
References: 43

Abstract

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.

Fields of Study & Subjects

DNA Repair Mechanisms Microtubule and mitosis dynamics Genetic Neurodegenerative Diseases

Publication details

Journal / source
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Volume
12
Issue
17
Pages
eadx9148–eadx9148
Publication date
24 April 2026
Language
EN