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SUMMARY: Younger isn’t always better: Why juvenile spermatocytes frequen
 tly mis-segregate their chromosomes - Francesca Cole\, University of Texas
  MD Anderson Cancer Center
DTSTART:20180523T090000Z
DTEND:20180523T100000Z
UID:TALK105736@talks.cam.ac.uk
CONTACT:Ian Henderson
DESCRIPTION:Maciej J. Zelazowski (1)\, Rhea Kang (1\,2)\, Lakshmi Paniker 
 (1)\, Mathilde Biot (1)\, Maria Sandoval1\,\nTolkappiyan Premkumar (1)\, L
 orie Leyva1\, and Francesca Cole (1\,2)+\n\n(1) Department of Epigenetics 
 and Molecular Carcinogenesis\, The University of Texas MD Anderson Cancer 
 Center\, Smithville\, Texas\, USA.  (2) Program in Epigenetics and Molecul
 ar Carcinogenesis\, Graduate School of Biomedical Sciences\, The Universit
 y of Texas MD Anderson Cancer Center\, Smithville\, TX 78957\, USA.   +Cor
 responding author\n\nFaithful chromosome segregation in meiosis requires c
 rossover (CO) recombination\, which is regulated to ensure at least one CO
  per homolog pair. We investigate failure to ensure COs in juvenile male m
 ice. By monitoring recombination genome-wide using cytological assays and 
 at hotspots using molecular assays\, we show that juvenile mouse spermatoc
 ytes have fewer COs relative to adults. Analysis of recombination in the a
 bsence of MLH3 provides evidence for greater utilization in juveniles of p
 athways involving structure-selective nucleases and/or alternative complex
 es\, which can act upon precursors to generate noncrossovers (NCOs) at the
  expense of COs. By analyzing the timing of recombination\, we show that t
 hese alternative pathways normally act late in meiotic prophase after most
  COs are formed. By contrast\, in juvenile mouse spermatocytes these alter
 native pathways are preciously active and can act upon common CO precursor
 s. We propose that some designated CO sites fail to mature efficiently in 
 juveniles owing to inappropriate activity of these alternative repair path
 ways\, leading to chromosome mis-segregation. We also find lower MLH1 focu
 s density in juvenile human spermatocytes\, suggesting that weaker CO matu
 ration efficiency may explain why younger men have higher risk of fatherin
 g children with Down syndrome.
LOCATION:Large Lecture Theatre\, Department of Plant Sciences
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