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Bub1/BubR1 and SAC 강재승 April 25th
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Bub1/BubR1 and SAC Introduction
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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
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Spindle Assembly Checkpoint
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Bub1 mutation & Cancer
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BubR1 mutation & Cancer
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Bub1/BubR1 and SAC Functions of BUB1/BUBR1
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Finding of Bub1: Yeast mutant
Budding Uninhibited by Benzimidazole Benzimidazole: spindle assembly inhibitor
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Finding of Bub1: Yeast mutant
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Finding of BubR1: Bub-related
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Function of Bub1/BubR1
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Function of Bub1/BubR1
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Blinkin: Bub1-recruting protein
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Blinkin: Bub1-recruting protein
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Blinkin: Bub1-recruting protein
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APC/C Regulation by BubR1
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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
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APC/C Regulation by BubR1
Ubiquitination activity
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APC/C, BubR1 and MCC MCC: Mitotic checkpoint complex
Protein complex consists of: BubR1 Bub3 CDC20 MAD2
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Sum.: Role of Bub1/BubR1 in SAC
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Bub1/BubR1 and chromosome
Chromosome congression is interrupted by Bub1/BubR1 knockdown.
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Bub1/BubR1 and SAC Current issues
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Structure of Bub1/BubR1
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Structure of Bub1/BubR1
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Structure of Bub1/BubR1
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Controversy: Bub1/BubR1 as kinase
Kinase domain Microtubule attachment vs. Chromosome congression Highly important for sac vs. auxillary
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Future research topics
Chromosome congression mechanism Bub1/BubR1-like proteins and SAC Ex) Neuron progenitor cell migration
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