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SUMMARY:Local and Global Regulation of Meiotic Prophase by Post-Translatio
 nal Protein Modification - Neil Hunter
DTSTART:20141215T161500Z
DTEND:20141215T180000Z
UID:TALK52788@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:Meiosis is the conduit of heredity\, producing haploid gametes
  containing mosaics of their precursor genomes. Gamete quality control inv
 olves regulatory processes that mediate successful execution of a variety 
 of chromosomal processes including pairing and synapsis\, homologous recom
 bination\, and spindle alignment. Despite these regulatory processes\, err
 ors in meiotic chromosome segregation are alarmingly common in humans\, es
 pecially in females. The ensuing aneuploid gametes are responsible for a l
 arge fraction of the estimated 1 million pregnancy miscarriages that occur
  in the U.S. each year.\nOne focus of our research is to understand how th
 e unique events of meiotic prophase are regulated by post-translational pr
 otein modification. Our current emphasis is the regulation of protein dyna
 mics by SUMO\, ubiquitin and phosphorylation. At a local level\, these mod
 ifications are differentially applied and integrated to control the outcom
 e of homologous recombination and ensure that all chromosome pairs undergo
  crossing over\, as required for accurate chromosome segregation at the fi
 rst meiotic division. More globally\, we find that ubiquitylation generall
 y accelerates the turnover of chromosome-associated recombination factors\
 , to promote the progression of recombination and its coordination with ch
 romosome synapsis. Finally\, at the cellular level\, we have discovered th
 at SUMOylation plays an essential role to promote apoptosis of oocytes tha
 t have experienced defects in chromosome synapsis and/or recombination. As
  such\, SUMOylation plays a central role in oocyte quality control and det
 ermination of ovarian reserve.\nMy talk will be focused around an interdep
 endent pair of RING-domain E3 ligases\, RNF212 and HEI10 (a.k.a. CCNBIP1)\
 ; and the MutSγ complex (Msh4-Msh5)\, a meiosis-specific recombination fa
 ctor. Intriguingly\, alleles of all three factors are associated with heri
 table variation in recombination rate in humans.\n
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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