Getting down to the phosphorylated ‘ nuts and

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Getting down to the phosphorylated ‘ nuts and bolts ‘ of spindle check point signalling : 

Getting down to the phosphorylated ‘ nuts and bolts ‘ of spindle check point signalling Dr. Anand R Trends in Biochemical sciences, 35; 2010

Cell cycle and Checkpoints : 

Cell cycle and Checkpoints Checkpoints - regulated transition points where progression to next phase be arrested by negative signals, incase of defect.

Slide 4: 

SPINDLE ASSEMBLY CHECKPOINT Pathway monitoring the fidelity of chromosome segregation in Mitosis Active in prometaphase; prevents precocious separation of sister chromatids Delays anaphase onset until chromosome biorientation

KINETOCHORE : 

KINETOCHORE

MECHANISM OF CHECKPOINT ACTION : 

MECHANISM OF CHECKPOINT ACTION

Unattached kinetochore activates SAC : 

Unattached kinetochore activates SAC

Slide 14: 

Generation of MCC 1 2 ???

APC/Cyclosomemachine designed to destroy!! : 

APC/Cyclosomemachine designed to destroy!! a cullin–RING-finger ubiquitin ligase Multisubunit complex; MW 1.5 MDa the cullin domain of Apc2 is associated with the RING-finger domain of Apc11 2 large domains- platform; arc lamp 2 coactivators – Cdc20; Cdh1

Functioning of APC/Cyclosome : 

Functioning of APC/Cyclosome

Models for APC/C inhibition : 

Models for APC/C inhibition

SAC Kinases : 

SAC Kinases

SILENCING OF CHECKPOINT : 

SILENCING OF CHECKPOINT

PROTEIN STRIPPING : 

PROTEIN STRIPPING

PP1 induced inactivation : 

PP1 induced inactivation

Slide 29: 

Inactivation by p31comet Energy dependent complex dissociation

Slide 30: 

Turning off kinases

Feedback circuit at SAC : 

Feedback circuit at SAC

Significance : 

Significance Aneuploidy – discrepancies in chromosome number Tumorigenesis

Take home….. : 

Take home….. Even a single unattached kinetochore could generate ‘wait anaphase’ signal APC activation needed for both progression to anaphase and exit from mitosis Cdc 20- activator of APC MCC – effector of SAC SAC mode of action targets Cdc 20