The Cell Cycle

The Cell Cycle

Eucaryotic Cell Cycle

Cell -Cycle Control System• the organization and control of the cell cycle is essentially the same in all eucaryotic cells

G0 Phase

Cell Cycle Clock

• The cell cycle clock uses a group of protein kinases to execute the various steps of cell cycle progression.

• The kinases used by the cell cycle machinery are called collectively cyclin-dependent kinases (CDKs).

• Cyclin levels oscillate during the cell cycle with cyclin mRNA and protein expression peaking at the time of maximum kinase activation.

• Cyclin degradation is triggered by ubiquitin ligases which leads to proteolytic breakdown in the proteosomes.

Activation of Cyclin-CDK complex

CDKs Activity Regulated by Cyclin Degradation

Cell Cycle Checkpoints

• regulation of the cell cycle also involves inhibitors of the cyclin-CDK complexes

S-Cdk Triggers DNA Synthesis

DNA Damage Checkpoints

• checkpoints in G1 and S phase prevent cells with DNA damage from starting or completing replication

• DNA damage increases p53 which increases the transcription of p21

• if the DNA damage is not repaired p53 may trigger apoptosis

M-Cdk Controls Entry into Mitosis

Mitosis

• prior to mitosis the chromosomes replicate and the sister chromatids are held together by cohesion rings

• condensins help to coil the mitotic chromatids

The cytoskeleton plays a central role in mitosis and cytokinesis• mitotic spindleo microtubuleso microtubule-associated motor proteins• contractile ringo actino myosin

Mitotic Spindle

• the centrosome is the microtuble-organizing center and duplicates prior to the M phase• at the beginning of mitosis the two centrosomes separate and the asters form• the mitotic spindle begins to form in prophase• dynamic instability• spindle poles and interpolar

microtubules

• the disassembly of the nuclear envelop occurs in prometaphase • spindle microtubles attach to the chromosomes through the kinetochores• the number of microtublules attached to each kinetochore varies among species – humans 20-40

• Metaphase is marked by the formation of the metaphase plate

• Anaphase begins with the release of the cohesion linkage by separase • securin inactivates separase and is removed by anaphase-promoting complex

• at telophase the mitotic spindle disassembles and the nuclear envelope reassembles

• in animal cells, cytokinesis involves the formation of the cleavage furrow

• cytokinesis in plant cells is guided by the phragmoplast

NecrosisApoptosis

Apoptosome

Anti-apoptotic Signal s• Bcl 2 • Bcl –XL

• A1

Pro-apoptotic Signals• Bax• Bak• Bid

• Mitogens stimulate cell division

• Growth Factors stimulate cells to grow