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Mitotic events - early

• Import of cyclin B1-cdk1.• Disassembly of the nuclear lamina.• Chromosome condensation.• Dissociation of cohesins from chromatid arms.• Separation of centrosomes and assembly of the

mitotic spindle.• Bipolar attachment of the spindle to the

chromosomes.• Release of the mitotic checkpoint.

Mitotic events - early

• Import of cyclin B1-cdk1.• Disassembly of the nuclear lamina.• Chromosome condensation.• Dissociation of cohesins from chromatid arms.• Separation of centrosomes and assembly of the mitotic

spindle.• Bipolar attachment of the spindle to the chromosomes.• Release of the mitotic checkpoint.

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Mitotic events - early

• Import of cyclin B1-cdk1.• Disassembly of the nuclear lamina.• Chromosome condensation.• Dissociation of cohesins from chromatid arms.• Separation of centrosomes and assembly of the mitotic

spindle.• Bipolar attachment of the spindle to the chromosomes.• Release of the mitotic checkpoint.

Mitotic events - early

• Import of cyclin B1-cdk1.• Disassembly of the nuclear lamina.• Chromosome condensation.• Dissociation of cohesins from chromatid arms.• Separation of centrosomes and assembly of the mitotic

spindle.• Bipolar attachment of the spindle to the chromosomes.• Release of the mitotic checkpoint.

The three factors that enable sister chromatid separation

• The pulling force - the mitotic spindle

• The glue - cohesins

• The timing mechanism - spindle checkpoint

Condensins replace cohesins in early mitosis

Mitotic events - early

• Import of cyclin B1-cdk1.• Disassembly of the nuclear lamina.• Chromosome condensation.• Dissociation of cohesins from chromatid arms.• Separation of centrosomes and assembly of the mitotic

spindle.• Bipolar attachment of the spindle to the chromosomes.• Release of the mitotic checkpoint.

Centrosome separation

G1

G2

Prophase

Mitotic events - early

• Import of cyclin B1-cdk1.• Disassembly of the nuclear lamina.• Chromosome condensation.• Dissociation of cohesins from chromatid arms.• Separation of centrosomes and assembly of the mitotic

spindle.• Bipolar attachment of the spindle to the chromosomes.• Release of the mitotic checkpoint.

Fluorescent mad2 on centromeres

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Mitotic events - metaphase

• Activation of the APC/C - degradation of securin - cleavage of Scc1 - Metaphase transition

The story of the two blind men

• Two blind men go into a shop and buy each five different pairs of socks. Unfortunately all ten pairs were packed in the same bag.

• How can the two men separate the socks so that each of them will get five pairs ?

Sister chromatid separation from prometaphase to anaphase

Securin

Separin

Cohesin

metaphase

Securin

Separin

Cohesin

prometaphase

APC

Check

point

Separin

anaphase

APC

Securin

Separin

Non-degradable securin does not prevent cytokinesisbut interferes with complete chromatide separation

histon-GFP Hoechst HeLa

securin

securinKAA-DM

securinKAA-DM

NIH3T3

Time lapse photography of cells expressing non-degradable securin

There is no problem to enter mitosis however at the metaphase transition trouble starts:

Some cell manage relatively well but remain connected by a thin thread of chromatin.

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Time lapse photography of cells expressing non-degradable securin

Some cells just give up and decondense their DNA without dividing at all.

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Mitotic events - late

• Activation of the APC/C - degradation of securin - cleavage of Scc1 - Metaphase transition

• Chromatid segregation.• Degradation of cyclin B1• Reassembly of the nuclear lamina.• Chromosome decondensation.• Cytokinesys

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The Polo kinases

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