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SUMMARY:Chromosome Segregation and Genome Stability - David Pellman\, Dana
 -Farber Cancer Institute\, Harvard Medical School
DTSTART:20120216T130000Z
DTEND:20120216T140000Z
UID:TALK32823@talks.cam.ac.uk
CONTACT:Kate Davenport
DESCRIPTION:Chromosome instability (CIN) is a hallmark of many tumors and 
 correlates with the presence of extra centrosomes1-4. However\, a direct m
 echanistic link between extra centrosomes and CIN has not been established
 . It has been proposed that extra centrosomes generate CIN by promoting mu
 ltipolar anaphase\, a highly abnormal division that produces 3 or more ane
 uploid daughter cells. Here\, we use long-term live-cell imaging to demons
 trate that cells with multiple centrosomes rarely undergo multipolar cell 
 divisions\, and the progeny of these divisions are typically inviable. Thu
 s\, multipolar divisions cannot explain observed rates of CIN. By contrast
 \, we observe that CIN cells with extra centrosomes routinely undergo bipo
 lar cell divisions\, but display a significantly elevated frequency of lag
 ging chromosomes during anaphase. To define the mechanism underlying this 
 mitotic defect\, we generated cells that differ only in their centrosome n
 umber. We demonstrate that extra centrosomes alone are sufficient to promo
 te chromosome missegregation during bipolar cell division.\nThese segregat
 ion errors are a consequence of cells passing through a transient ‘multi
 polar spindle intermediate’ in which merotelic kinetochore-microtubule a
 ttachment errors accumulate prior to centrosome clustering and anaphase. T
 hese findings provide a direct mechanistic link between extra centrosomes 
 and CIN\, two common characteristics of solid tumors. We propose that this
  mechanism may be a common underlying cause of CIN in human cancer.\n
LOCATION:Cancer Research UK Cambridge Research Institute\, Lecture Theatre
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