Regulations of the cell cycle

CHECKPOINTS 

• Control progress through cell cycle
• Prevent cells entering next stage until previous stage completed
• G1: DNA damage
• S: Incomplete replication
• G2: DNA damage
• M: Ensure all necessary earlier events been performed

MECHANISMS OF REGUATION

• Regulators: Phosphorylation. Dephosphorylation
• M-phase kinase
• Regulates mitosis
• 2 forms. Phosphorylation of proteins
• Activation at G2/M 
• Inactivation before end of M
• 2 subunits
• Catalytic
• Cdc2
• Kinase phosphorylates serine and threonine
• Modification ￫ Triggers G2 to M
• Regulatory
• Cyclin
• Necessary for catalytic kinase to function on right substrates
• Destruction by proteolysis ￫ Inactivation of M-phase kinase
• Substrate: H1 histone
• Checkpoint pathways 
• Prevent progression if DNA is damaged
• Recognition of DNA damage
• Apoptosis. Block cell cycle. Transcribe response genes. Repair damage
• Appropriate progress made
• Replication before division. Kinetochores paired before metaphase finished
• Proteins involved
• Sensor
• Recognise event that triggers checkpoint pathway
• Transducer
• Activated by sensors
• Amplification function
• Effector
• Activated by transducer kinases
• Correct the event triggered the checkpoint pathway
• Protein kinase ATM. Ataxia telangiectasia
• Cyclin-dependent kinases (CKDs) 
• Progression of cell cycle regulated by kinases that interact with cyclins
• Inhibitors
• Cyclin-dependent kinase inhibitors (CKIs)
• Retinoblastoma gene product phosphorylated by cdm-cyclin D complex
• Action of CKI of INK4 family
• Action of CKI of Kip family
• Mutations ￫ Cancers