Genetic Dissection of Crossover Mutants Defines Discrete Intermediates in Mouse Meiosis

Authors

Tolkappiyan Premkumar
Lakshmi Paniker
Rhea Kang
Mathilde Biot
Ericka Humphrey
Honorine Destain
Isabella Ferranti
Iyinyeoluwa Okulate
Holly Nguyen
Vindhya Kilaru
Melissa Frasca
Parijat Chakraborty
Francesca Cole

Publication Date

8-17-2023

Journal

Molecular Cell

Abstract

Crossovers (COs), the exchange of homolog arms, are required for accurate chromosome segregation during meiosis. Studies in yeast have described the single-end invasion (SEI) intermediate: a stabilized 3' end annealed with the homolog as the first detectible CO precursor. SEIs are thought to differentiate into double Holliday junctions (dHJs) that are resolved by MutLgamma (MLH1/MLH3) into COs. Currently, we lack knowledge of early steps of mammalian CO recombination or how intermediates are differentiated in any organism. Using comprehensive analysis of recombination in thirteen different genetic conditions with varying levels of compromised CO resolution, we infer CO precursors include asymmetric SEI-like intermediates and dHJs in mouse. In contrast to yeast, MLH3 is structurally required to differentiate CO precursors into dHJs. We verify conservation of aspects of meiotic recombination and show unique features in mouse, providing mechanistic insight into CO formation.

Keywords

Animals, Mice, Saccharomyces cerevisiae, Meiosis, Chromosome Segregation, DNA, Cruciform, Mammals

Comments

Supplementary Materials

PMID: 37595556