Dimerization of the S. cerevisiae Spo11 core complex.

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Spo11 initiates meiotic recombination by creating DNA double-strand breaks (DSBs) through a topoisomerase-like mechanism.
• Unlike its relative Topo VI, Spo11 does not form stable dimers, a feature thought to prevent uncontrolled DNA cleavage.

Purpose of the Study:

• To investigate the dimerization of *Saccharomyces cerevisiae* Spo11 in complex with its partners Ski8, Rec102, and Rec104.
• To understand the role of Spo11 dimerization in initiating meiotic recombination and DSB formation.

Main Methods:

• Investigated Spo11 complex dimerization using duplex and branched DNA substrates.
• Employed AlphaFold modeling to guide mutagenesis of the Spo11 dimer interface.
• Assessed the impact of mutations on DNA double-strand break (DSB) formation.
• Characterized the DNA-binding and dimerization functions of Rec102.

Main Results:

• The Spo11 complex forms transient, unstable dimers on DNA substrates.
• Mutagenesis of the Spo11 dimer interface did not significantly impair DSB formation, suggesting additional in vivo dimerization factors.
• Rec102 demonstrated essential DNA-binding and catalytic functions.
• Rec102 was found to participate in dimerization via trans contacts with Ski8.

Conclusions:

• Spo11 dimerization is transient and unstable, involving interactions with Ski8, Rec102, and Rec104.
• Rec102 is crucial for both DNA binding and dimerization, playing a key role in Spo11 complex assembly and function.
• The study provides novel insights into the mechanism of Spo11-mediated meiotic recombination initiation.