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

Area of Science:

• Genetics
• Molecular Biology
• Cell Biology

Background:

• Meiotic crossover (CO) formation is vital for genetic diversity and accurate chromosome segregation.
• CO formation involves designating double-strand breaks and resolving Holliday junctions (HJs).
• The functional link between CO designation and resolution machinery was previously unclear.

Purpose of the Study:

• To elucidate the mechanism coupling CO designation with HJ resolution.
• To investigate the role of COSA-1 in coordinating these meiotic processes.

Main Methods:

• Investigated protein-protein interactions between COSA-1 and SLX-4.
• Utilized genetic disruption of the COSA-1/SLX-4 interaction.
• Assessed meiotic recombination intermediates and CO formation.
• Employed artificial tethering of SLX-4 to CO designation proteins for rescue experiments.

Main Results:

• COSA-1 directly interacts with the SLX-4 scaffold protein, which organizes HJ resolvases (SLX-1, XPF-1, MUS-81).
• Disrupting this interaction leads to unrepaired recombination intermediates and defective CO formation.
• Artificial tethering of SLX-4 rescued these defects, highlighting the importance of physical proximity.
• COSA-1 was shown to promote the assembly of the SLX-4 resolvase complex.

Conclusions:

• CO designation proteins, like COSA-1, directly recruit the HJ resolution machinery.
• This interaction ensures accurate CO formation by coupling designation and resolution steps.
• The findings support a conserved mechanism for coordinating meiotic recombination and chromosome segregation.