Bub1/BubR1 and SAC 20128001 강재승 April 25th.

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Presentation transcript:

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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