13: metaphase, anaphase, telophase, cytokenisis

Kinetochores

• large protein assemblies on chromosomes' centromeres

• where spindle microtubules bind to chromosomes

• ensure proper chromosome segregation

(image: red dots = kinetochores)

metaphase

• Chromosomes align in the middle of the spindle.

• Kinetochores attach to spindle microtubules, with one kinetochore attached to each pole.

• Tension at kinetochores ensures proper attachment

Spindle Assembly Checkpoint (SAC)

• Ensures proper chromosome alignment before anaphase.

• If microtubules are depolymerised (nocodazole) or stabilised (taxol), checkpoint blocks anaphase.

• Unattached kinetochores activate SAC, delaying anaphase.

• SAC proteins removed by cytoplasmic dynein once all kinetochores are attached => move on to anaphase

aneuploid daughters

daughter cells that have wrong number of chromosomes

Metaphase to Anaphase Transition: cohesins and separases

• chromosomes are replicated in S-phase => 2 sister chromatids

• sister chromatids stick together via cohesins

• at anaphase, sister chromatids separate as cohesins are cleaved by separase enzymes

Metaphase to Anaphase Transition: anaphase promoting complex (APC/C)

• APC/C triggers proteolysis of specific proteins by binding to them (like a tag):

  • covalently attaches ubiquitin (ubiquitylation)

  • this tagging directs proteins to the proteasome for degradation

What is M-Cdk and what does it do?

• M-Cdk (Mitosis Cyclin-Dependent Kinase) = Cyclin B + Cdk1.

• Function: Controls entry into mitosis (M phase) by triggering:

• Chromosome condensation.

• Spindle formation.

• Nuclear envelope breakdown.

• Regulation:

• Activated when Cyclin B binds to Cdk1.

• Inactivated when APC/C degrades Cyclin B, allowing the cell to exit mitosis.

metaphase to anaphase transition summary

Anaphase A

• Anaphase A:

• Sister chromatids move towards spindle poles.

• Kinetochore microtubules depolymerise (shorten) at + ends, pulling chromatids apart.

Anaphase B

• Spindle poles move apart.

• Eg5 kinesin pushes centrosomes apart.

• Dynein at the cortex pulls spindle poles apart.

anaphase a + b main difference

• Anaphase A = Chromosomes move toward poles.

• Anaphase B = Spindle poles move apart, stretching the cell.

telophase

• Nuclear envelope reassembles.

• Nuclear lamins reform (M-Cdk is inactive).

• Golgi apparatus reassembles

• secretion and endocytosis restart.

cytokinesis

• Contractile ring of actin and myosin II forms.

• The ring contracts to form a cleavage furrow, splitting the cell.

• Integrins are phosphorylated, weakening cell attachment to the surface.