M/A: Spindle assembly checkpoints Empirical observations: arrest of mitotic progress in presence of spindle poisons (e.g., colcemid) Delay of mitotic progress.

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Presentation transcript:

M/A: Spindle assembly checkpoints Empirical observations: arrest of mitotic progress in presence of spindle poisons (e.g., colcemid) Delay of mitotic progress in presence of unattached or mal-oriented chromosome Much experimental evidence for a tension-sensitive checkpoint especially from experiments involving chromosome micromanipulation (Nicklas)

The mitotic spindle

Normal chromosome orientation

Error and correction

Experimental “correction”

Attachment error

Role of tension revealed

Spindle checkpoint: diffusible APC inhibitor Dominant action of single unattached kinetochore suggests diffusible inhibitor Conserved checkpoint protein Mad2p (MAD2) localized to kinetochores, but diffusible inhibits the APC quantitatively depleted as kinetochores become stably attached in bipolar orientation

Components of spindle assembly checkpoint(s) Diffusible anaphase inhibitor MAD2 and interacting proteins Protein or complex that “proofreads” the spindle assembly ILP1 kinase (aurora kinase) - tension-sensitive Protein or protein complex that secures interactions between microtubules and chromatids DNA and protein binding proteins (DASH?)