Abstract
Meiosis relies on the SPO11 endonuclease to generate the recombinogenic DNA double strand breaks (DSBs) required for homologous chromosome synapsis and segregation. The number of meiotic DSBs needs to be sufficient to allow chromosomes to search for and find their homologs, but not excessive to the point of causing genome instability. Here we report that the mammal-specific gene Tex19.1 promotes Spo11-dependent recombination in mouse spermatocytes. We show that the chromosome asynapsis previously reported in Tex19.1-/- spermatocytes is preceded by reduced numbers of recombination foci in leptotene and zygotene. Tex19.1 is required for normal levels of early Spo11-dependent recombination foci during leptotene, but not for upstream events such as MEI4 foci formation or accumulation of H3K4me3 at recombination hotspots. Furthermore, we show that mice carrying mutations in Ubr2, which encodes an E3 ubiquitin ligase that interacts with TEX19.1, phenocopy the Tex19.1-/- recombination defects. These data suggest that Tex19.1 and Ubr2 are required for mouse spermatocytes to accumulate sufficient Spo11-dependent recombination to ensure that the homology search is consistently successful, and reveal a hitherto unknown genetic pathway promoting meiotic recombination in mammals.
Highlights
Recombination plays key roles in meiosis and gametogenesis through facilitating the pairing and reductional segregation of homologous chromosomes, and by increasing genetic variation in the generation
Meiosis is a specialised type of cell division that occurs during sperm and egg development to reduce chromosome number prior to fertilisation
This study identifies a genetic pathway required to generate robust meiotic recombination in mouse spermatocytes
Summary
Recombination plays key roles in meiosis and gametogenesis through facilitating the pairing and reductional segregation of homologous chromosomes, and by increasing genetic variation in the generation. Meiotic recombination is initiated when programmed DNA double strand breaks (DSBs) are generated during the leptotene stage of the first meiotic prophase. Meiotic DSBs recruit a series of recombination proteins visualised cytologically as recombination foci, and initiate a search for homologous chromosomes thereby promoting homologous chromosome synapsis during zygotene. Crossovers exchange large tracts of genetic information between parental chromosomes, increasing genetic diversity in the population. These crossovers, which physically manifest as chiasmata, hold homologs together after they desynapse in diplotene and help to ensure that homologous chromosomes undergo an ordered reductional segregation at anaphase I [1,2]
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