Directional branch migration remodels the meiotic Holliday junction landscape

Area of Science:

• Genetics
• Molecular Biology
• Cell Biology

Background:

• Holliday junctions (HJs) are critical DNA structures in homologous recombination and double-strand break (DSB) repair.
• Meiotic crossovers, derived from HJs, are essential for accurate chromosome segregation during meiosis.
• Genome-wide mapping of meiotic HJs has been a significant challenge.

Purpose of the Study:

• To develop and apply a novel method for the genome-wide mapping of meiotic Holliday junctions.
• To investigate the dynamic behavior and genomic distribution of HJs during meiosis.
• To understand the relationship between HJ dynamics, transcription, and crossover formation.

Main Methods:

• Development of a HJ-binding peptide approach (HJSeq) for capturing and mapping HJs.
• Genome-wide analysis of HJ distribution and migration patterns during the pachytene stage of meiosis.

Main Results:

• HJSeq successfully enabled the first genome-wide mapping of meiotic HJs.
• HJs exhibit sustained, directional branch migration during pachytene, moving away from DSB sites.
• HJ migration is linked to transcription, occurring towards convergent transcription sites.
• HJ formation propensity correlates with DSB hotspot strength.

Conclusions:

• Pachytene is an active phase of HJ remodeling, accommodating the chromatin environment.
• Transcription-linked HJ branch migration supports regulated crossover formation.
• Faithful chromosome segregation relies on dynamic HJ remodeling during meiosis.