Special seminar

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Sep 27, 2018, 2:01:56 AM9/27/18
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Dear all,


There will be a Special Seminar by a visitor, Dr. Nishant K T, from IISER-TVM as per the following schedule:

 

Date: 28-9-2018

Time: 11 am

Venue: BT Seminar Hall

 

Title: Meiotic recombination: mechanisms, distribution and role in chromosome segregation


Abstract: 

Segregation of homologous chromosomes during the first meiotic division requires at least one obligate crossover/exchange event between the homolog pairs.  In the baker’s yeast Saccharomyces cerevisiae and mammals, the mismatch repair related factors, Msh4-Msh5 and Mlh1-Mlh3 generate majority of the meiotic crossovers from programmed  Double Strand Breaks (DSBs).  By genome wide analysis of meiotic recombination in msh4 hypomorphs and mlh3 mutants in S. cerevisiae, we show that even though these mutants  make four times as many crossovers (~64) as the number of chromosomes (16), the obligate crossover is perturbed.  These results suggest that variation in crossover frequencies can compromise the obligate crossover and also support a mechanistic role for crossover distribution mechanisms in obligate crossover formation.   We also demonstrate enhanced non-crossovers in mlh3 point mutants providing new insights into how meiotic recombination outcomes are regulated.


              To understand the mechanistic role of Msh4-Msh5 in meiotic crossing over, we performed genome wide ChIP-sequencing and cytological analysis of the Msh5 protein in cells synchronized for meiosis.  We found that the initial recruitment of Msh4-Msh5 occurs following DSB resection.  A two-step Msh5 binding pattern was observed: an early weak binding at DSB hotspots followed by enhanced late binding upon formation of double Holliday junction structures.  Msh5 preferentially binds strong DSB hotspots away from the chromosome axis and is depleted at chromosome axis sites.  These data have implications for how Msh4-Msh5 may work with Mlh1-Mlh3 to ensure Holliday junction resolution at the chromosome axis.  Together, these results shed novel insights into the mechanisms of meiotic recombination, distribution and its role in chromosome segregation. 
 



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