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Biot, M.

Publications and source records attributed to Biot, M..

2 recordsLinked to original sources

Fundamental principles of chromosome organization for meiotic recombination

In meiotic cells, chromosomes are organized as chromatin loop arrays anchored to a protein axis. This organization is essential to regulate meiotic recombination, from DNA double-strand break (DSB) formation to their repair 1. In mammals, it is unknown how chromatin loops are organized along the genome and how proteins participating in DSB formation are tethered to the chromosome axes. Here, we identified three categories of axis-associated genomic sites: PRDM9 binding sites, where DSBs form 2, binding sites of the insulator protein CTCF, and H3K4me3-enriched sites. We demonstrated that PRDM9 promotes the recruitment of MEI4 and IHO1, two proteins essential for DSB formation 3,4. In turn, IHO1 anchors DSB sites to the axis components HORMAD1 and SYCP3. We discovered that IHO1, HORMAD1 and SYCP3 are associated at the DSB ends during DSB repair. Our results highlight how interactions of proteins with specific genomic elements shape the meiotic chromosome organization for recombination.

molecular biology↗

Genetic dissection of crossover mutants defines discrete intermediates in mouse meiosis

Crossovers, the exchange of homolog arms, are required for accurate segregation during meiosis. Studies in yeast have established that the single end invasion intermediate is highly regulated to ensure crossover distribution. Single end invasions are thought to differentiate into double Holliday junctions that are resolved by MutLgamma (MLH1/3) into crossovers. Currently, we lack knowledge of early steps of mammalian crossover recombination or how intermediates are differentiated in any organism. Using comprehensive analysis of recombination and cytology, we infer that polymerized single-end invasion intermediates and nicked double Holliday junctions are crossover precursors in mouse spermatocytes. In marked contrast to yeast, MLH3 plays a structural role to differentiate single end invasions into double Holliday junctions with differentially polymerized 3 ends. Therefore, we show independent genetic requirements for precursor formation and asymmetry with regard to 3 end processing, providing mechanistic insight into crossover formation and patterning.

genetics↗