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Bub1/BubR1 and SAC
20128001 강재승
April 25th
Bub1/BubR1 and SAC
INTRODUCTION
Spindle Assembly Checkpoint
• Checks if two microtubules are correctly
bound to centromere.
• If SAC does not work properly, aneuploidy
occurs in high rate.
• Bub1 and BubR1 are parts of SAC
Spindle Assembly Checkpoint
Bub1 mutation & Cancer
BubR1 mutation & Cancer
Bub1/BubR1 and SAC
FUNCTIONS OF BUB1/BUBR1
Finding of Bub1: Yeast mutant
• Budding Uninhibited by Benzimidazole
– Benzimidazole: spindle assembly inhibitor
Finding of Bub1: Yeast mutant
Finding of BubR1: Bub-related
Function of Bub1/BubR1
Function of Bub1/BubR1
Blinkin: Bub1-recruting protein
Blinkin: Bub1-recruting protein
Blinkin: Bub1-recruting protein
APC/C Regulation by BubR1
APC/C Regulation by BubR1
• APC/C: anaphase promoting complex
• Ubiquitin ligase
• Degrades securin/Activates seperase
– Seperase cleaves cohesin
• Low APC/C activity in hBubR1 fraction
APC/C Regulation by BubR1
• Ubiquitination activity
APC/C, BubR1 and MCC
• MCC: Mitotic checkpoint complex
• Protein complex consists of:
– BubR1
– Bub3
– CDC20
– MAD2
Sum.: Role of Bub1/BubR1 in SAC
Bub1/BubR1 and chromosome
• Chromosome congression is interrupted by
Bub1/BubR1 knockdown.
Bub1/BubR1 and SAC
CURRENT ISSUES
Structure of Bub1/BubR1
Structure of Bub1/BubR1
Structure of Bub1/BubR1
Controversy: Bub1/BubR1 as kinase
• Kinase domain
– Microtubule attachment vs. Chromosome
congression
– Highly important for sac vs. auxillary
Future research topics
• Chromosome congression mechanism
• Bub1/BubR1-like proteins and SAC
– Ex) Neuron progenitor cell migration
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