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SUMMARY:Feedback control of cell division - Andrea Musacchio\, Director\, 
 Department of Mechanistic Cell Biology\, Max-Planck Institute of Molecular
  Physiology 
DTSTART:20140918T151500Z
DTEND:20140918T170000Z
UID:TALK52782@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:Our work focuses on kinetochores\, large proteinaceous structu
 res that are built on the centromere region of chromosomes. In mitosis and
  in meiosis\, kinetochores provide chromosomes with a site of attachment t
 o spindle microtubules. They also control a cell cycle checkpoint\, the sp
 indle assembly checkpoint\, required to prevent mitotic exit prior to the 
 completion of chromosome bi-orientation. \nBiochemical reconstitution is p
 laying a leading role in developing an understanding of kinetochore organi
 zation. In recent years\, we have contributed to this effort by reconstitu
 ting several kinetochore sub-complexes that operate at the interface with 
 microtubules\, including the 4-subunit Ndc80 and Mis12 complexes\, and the
  2-subunit Knl1 complex. Whenever possible\, we have been using high- or m
 edium-resolution analysis to gain a structural understanding of these kine
 tochore complexes and have investigated the functional implications of our
  work. More recently\, we have extended our efforts to include a significa
 nt set of additional kinetochore subunits that are positioned more interna
 lly in the kinetochore\, at the interface with chromatin. I will report on
  these recent efforts. \nUnderstanding how kinetochores control dynamicall
 y the checkpoint response in relation to their attachment to microtubules 
 is also an interesting and important challenge. We are therefore testing t
 he ability of the reconstituted kinetochore complexes to interact with dif
 ferent checkpoint proteins. For instance\, we are in the process of charac
 terizing the complex interactions of the Bub1 and BubR1 proteins with Knl1
 \, using Saccharomyces cerevisiae and human cells as model systems. In my 
 seminar\, I will report on these current efforts. \n\nLast resort readings
 \nPetrovic A\, Mosalaganti S\, Keller J\, Mattiuzzo M\, Overlack K\, Krenn
  V\, De Antoni A\, Wohlgemuth S\, Cecatiello V\, Pasqualato S\, Raunser S 
 & Musacchio A (2014) Modular Assembly of RWD Domains on the Mis12 Complex 
 Underlies Outer Kinetochore Organization. Mol Cell 53:591-605. doi: 10.101
 6/j.molcel.2014.01.019.\nKrenn V\, Overlack K\, Primorac I\, van Gerwen S 
 & Musacchio A (2014) KI motifs of human Knl1 enhance assembly of comprehen
 sive spindle checkpoint complexes around MELT repeats. Curr Biol 24:29-39.
  doi: 10.1016/j.cub.2013.11.046. \nPrimorac I\, Weir JR\, Chiroli E\, Gros
 s F\, Hoffmann I\, van Gerwen S\, Ciliberto A & Musacchio A (2013) Bub3 re
 ads phosphorylated MELT repeats to promote spindle assembly checkpoint sig
 naling\, Elife 2:e01030. doi: 10.7554/eLife.01030.\n
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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