[BIO Colloquium] Chromosome instability and cancer
  • Hyunsook Lee, Ph.D. (Seoul National University)
  • SLS Colloquia / Apr 29th 04:00 pm / AMRB 113
Abstract
 

BubR1 acetylation is essential in mitosis.  To reveal the physiological roles of BubR1 acetylation, we generated an acetylation-deficient BubR1 allele (K243R) in mice using knock-in strategy.  Here we report that BubR1 acetylation is required for chromosome-spindle attachment, as well as spindle assembly checkpoint (SAC) maintenance.  Homozygous mutant mice exhibit early embryonic lethality, however the mice heterozygous for the acetylation-deficient BubR1 allele (K243R/+) survive without any developmental defects.  Unlike hypomorphic BubR1 mice (mice expressing BubR1 with reduced levels), K243R/+ mice do not display premature aging phenotype but spontaneously developed tumors with massive chromosome mis-segregations.  Thorough analysis of the heterozygous mice and MEFs revealed that BubR1 acetylation is involved in counteracting excessive Aurora B activity or chromosome congression.  As we reported previously, BubR1 acetylation is essential in SAC activity.  Particularly, analysis of the mutant mice revealed that it was involved in the maintenance of SAC, and not the initiation of SAC signal.  We discuss that the combined effects of failure in chromosome-spindle attachment and weakened SAC cause genetic instability and cancer in K243R/+ mice.

Download : UNIST2014.doc