Spatial control of Cell Division Flashcards
Function of Mps1
Localises the kinetocore
Recruits other proteins and assembles them into an inhibitory complex (MCC)
Components of the mitotic checkpoint
Mps1 kinase
Kinetochore
Mitotic checkpoint complex (MCC)
Anaphase promoting complex
Mitotic checkpoint complex (MCC) function
Inhibits a large ubiquitin ligase needed for mitotic exit
When does the mitotic checkpoint end?
When microtubules attach
What happens during the mitotic checkpoint
1) MPS1 is removed from kinetochores
2) Phosphatases are activated to dephosphorylate key checkpoint proteins
3) Microtubule motors strip the checkpoint proteins from the kinetochore down microtubules towards spindle pores
what does MPS1 bind to?
NDC80
What is NDC80 function?
Complex which binds microtubules at the kinetochore
How is SAC silencing caused?
Competition of Mps1 and microtubules for NDC80 as they bind at the same binding site
What is involved in error connection?
Aurora B
Centromere
Destabilisation of incorrect microtubule attachments
What does Aurora B do?
Localises to the centromere in the kinetochore
Phosphorylates the kinetochore to remove microtubules through the electrostastic charge
Kinetochores under tension are removed away from Aurora B activity and therefore stabilised
What is used to measure kinase activity?
FRET reporters
How does FRET analysis work?
FRET connected to the substrate motif of the kinase, it is phosphorylated and then the phosphorylation will allow it to bind to the phosphopeptide binding domain
What are the 5 different types of ways errors can occur in mitosis?
Weakened checkpoint Error correction defects Multipolar spindles Cohension defects Cytokinesis failure
What is a weakened checkpoint?
One chromosome is not divided
What is a error correction defect?
‘tug of war’ - one of the chromosomes is divided but is attached by both spindles