Cell division (1) cytoplasm nucleus Mitosis G1 phase S phase DNA replication G2 phase Cytokinesis Chromosome Segregation (Karyokinesis)

Cell division (2) DNA replication Chromosome segregation

time activity Cell division (3) replicate replicate replicate divide divide divide

Lessons from cell fusion (1) G1 phase Mitosis M-phase Promoting Factor

Lessons from cell fusion (2) S phase Mitosis M-phase Promoting Factor G1 phase S-phase S-phase Promoting Factor

Lessons from cell fusion (3) G1 phase G2-phase M-phase Delaying Factor S phase G2-phase DNA Re-replication Inhibitor

Interdependence DNA replication Chromosome segregation

Cyclins (1) cyclins MPF MPF mitosis mitosis interphase cyclins

time activity Cyclins (2) Replicate: Cyclin E Divide: Cyclin B Replicate: Cyclin E Divide: Cyclin B Replicate: Cyclin E Divide: Cyclin B

Cyclin/cdks G1 S M G2 cdk cdk cyclin cyclin G1 cyclin mitotic cyclin

Cyclin/cdks in mammals Cyclin D G2 S G1 S M G2 Cdk1 Cdk2 Cdk2 Cdk4 Cdk6 S Cyclin E M Cyclin A Cyclin B

Kinase activity G1 G2 S M Cyclin B /cdk1 (1) Cyclin B CyclinE-cdk2 CyclinA-cdk2 CyclinB-cdk1 Protein level

Cyclin B /cdk1 (2) CycB APC Ub Ub Ub Ub Ub Spindle Checkpoint APC E2F CycA cdk2 CycA CycB NF-Y B-Myb FoxM1 Kinase activity G1 G2 S M CyclinE-cdk2 CyclinA-cdk2 CyclinB-cdk1 Cyclin B Protein level

Cdk activation (1) Cyclin B Wee1 Cdc25 Cdk1 P P P CAK

CyclinB - kinase activity Cdk activation (2) Cdk1 P P Wee1 P CAK Cdc25 + + P P

Bistability (1) Cyclin B1 levels Cyclin B1-Cdk1 activity

Cyclin Bistability (2) Cdk P P Wee1 P CAK Cdc25 Plk1