University of Cambridge > Talks.cam > Plant Sciences Talks >  Younger isn’t always better: Why juvenile spermatocytes frequently mis-segregate their chromosomes

Younger isn’t always better: Why juvenile spermatocytes frequently mis-segregate their chromosomes

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Maciej J. Zelazowski (1), Rhea Kang (1,2), Lakshmi Paniker (1), Mathilde Biot (1), Maria Sandoval1, Tolkappiyan Premkumar (1), Lorie Leyva1, and Francesca Cole (1,2)+

(1) Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, USA . (2) Program in Epigenetics and Molecular Carcinogenesis, Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957 , USA. +Corresponding author

Faithful chromosome segregation in meiosis requires crossover (CO) recombination, which is regulated to ensure at least one CO per homolog pair. We investigate failure to ensure COs in juvenile male mice. By monitoring recombination genome-wide using cytological assays and at hotspots using molecular assays, we show that juvenile mouse spermatocytes have fewer COs relative to adults. Analysis of recombination in the absence of MLH3 provides evidence for greater utilization in juveniles of pathways involving structure-selective nucleases and/or alternative complexes, which can act upon precursors to generate noncrossovers (NCOs) at the expense of COs. By analyzing the timing of recombination, we show that these alternative pathways normally act late in meiotic prophase after most COs are formed. By contrast, in juvenile mouse spermatocytes these alternative pathways are preciously active and can act upon common CO precursors. We propose that some designated CO sites fail to mature efficiently in juveniles owing to inappropriate activity of these alternative repair pathways, leading to chromosome mis-segregation. We also find lower MLH1 focus density in juvenile human spermatocytes, suggesting that weaker CO maturation efficiency may explain why younger men have higher risk of fathering children with Down syndrome.

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