1 hr

10-12 hr

8 hr

4-6 hr (M)

Spindle-assembly checkpoint - confirms that all the chromosomes are properly attached to the spindles.

Resting phase (G0) – non-proliferative phase - can remain in for long periods of time. Common for fully differentiated cell.

Chromosome-segregation checkpoint - confirms that the chromosomes have segregated to the poles triggering division.

DNA damage checkpoint - prevents progression through the cell cycle until the damage is repaired. Arrests at G1,S and G2ATM and p53

G2 checkpoint – triggers entry into mitosis by maturation promoting factor (MPF) (formed from Cyclin B and CDC2) and activated by CDC 25. MPF= M Cyclin and M CDK

G1 checkpoint – is environment right for division?

G1-phase CDK’s

S-phase CDKs

Mitotic CDKs (MPF)

4. Mitotic cyclins trigger:• Chromosome condensation• Assembly of the mitotic

spindle• Breakdown of nuclear

envelope

ATM – checks DNA for damage. If it finds damage it activates Chk2 which phosphorylates CDC25 preventing it from activating MPF.It also stabilises p53 the guardian of the genome which can synthesis CKI’s, DNA repair enzymes and cause apoptosis

4. Synthesis of proteinsrequired for entryinto S phase

3. E2F transcription factorregulates expression ofspecific genes

E2FDNA

E2F

Rb

Retinoblastoma proteinprevents release of E2F

P Rb

2. Phosphorylation ofRb releases E2F

G1 CDK

G1 cyclin

1. G1 cyclinsactivate G1 CDKs

Growth factors inducesynthesis of G1 cyclins – GF RAS-GTPRAF MEK-PMAPK-PTF G1 cyclin

Replicationcomplex

G1 CDK

G1 cyclin

S CDK

S cyclinCKI

CKI CKICKI

CKI P

1. Phosphorylation of CKItriggers its degradation

S CDK

S cyclin

2. S-phase CDKs are activated by the release

of CKIs

3. Phosphorylation ofreplication complextriggers DNA synthesis

P

Growth inhibitory factors induce synthesis of CKIs – SMADSMAD-P SMAD-coSMADTF CKI

PM CDK

M cyclinInhibitoryphosphate

Phosphorylation of: Histones Microtubules Lamins

M CDK

M cyclin

2. Replication complex causes activation ofa phosphatase(CDC 25)

Replicationcomplex

Mitotic cyclins trigger: Chromosome condensation Assembly of the mitotic spindle Breakdown of nuclear envelope

1. Completion of DNA synthesisreleases replication complex

PM CDK

M cyclin

Inhibitoryphosphate

Phosphorylation of: Histones Microtubules Lamins

M CDK

M cyclin

2. Replication complex causes activation of a phosphatase

(CDC25)

Replicationcomplex

4. Mitotic cyclins trigger:• Chromosome condensation• Assembly of the mitotic spindle• Breakdown of nuclear envelope

1. Completion of DNA synthesisreleases replication complex

3. CDC25 phosphatase activates MPF (M CDK complex)