Regulations of the Cell Cycle

Internal Regulation of the Cell Cycle

Functional Limitations

1. Surface-to-volume ratio: when surface area is small compared to volume → cell growth stops or cell division begins
2. Genome-to-volume ratio: ability of genome to function is limited by by finite amount of genetic material

• Cell grows → volume increases but genome size stays constant → G/V decreases → cell doesn’t have enough material to regulate cellular activities
• Factors that regulate cell cycle become distorted → can lose control of production of growth enzymes → cells become cancerous

Molecular Regulation of Cell Cycle

1. Interactions between cyclins and cyclin-dependent kinases regulate the cell cycle & control checkpoints

• Cyclin: proteins whose levels fluctuate in cell cycle (highest at G2)
  • Function: phosphorylates (& combines) CDKs to regulate the cell cycle
• CDKs: kinase enzyme whose levels remain constant; activated by cyclins thru phosphorylation
  • Function: prepares for cell division & responsible for advancing cell past cell cycle checkpoints
• CDKs + Cyclins= Cyclin-CDK complexes such as Maturation Promoting Factor (MPF)
  • CDKs increase in lvls with cyclins

Purple Line: MPF activity

• Shows that it peaks at mitosis & drops again at every checkpoint                                                               

Red Line: Cyclin

• It “cycles”: builds up prior to mitosis, at its peak, then sharply drops

Maturation Promoting Factor

• Cyclin-CDK complex that advances cell cycle through G2 checkpoint by phosphorylating and activating proteins involved with chromosome condensation, nuclear envelope breakdown, spindle assembly and MPF self destruction (signals end of G2)
  • Is self-regulating because starts process that destroys its own cyclin

1. Checkpoints: specific points during cell cycle where cell evaluates internal and external conditions to determine whether or not to continue thru cell cycle

• Each checkpoint has a specific cyclin-cdk that advances the cell past it

G1 checkpoint – committed step: leads to cell division – checks cell size, growth factors, nutrients, and the environment – checks DNA, if damaged → repair → if failed triggers apoptosis **environment: external and internal controls that affect it If passed: Enter S phase → synthesize DNA, prepares to divide successfully If failed: Moves into G0

G2 checkpoint –          Checks if all DNA is replicated and repaired           If passed: Enters M phase (mitosis)

M Checkpoint – in metaphase and before anaphase – checks if all of the chromosomes are lined up properly in the middle of the cell and kinetochores are attached – ensures that you get equal distribution of chromosomes between the two cells If Passed: Enters Anaphase   If Failed: Can pause stage until stray chromosomes corrected or trigger apoptosis

External Factors that regulate cell cycle/production of cdks

• Growth factors: proteins released by certain cells that stimulate other cells to divide
• Density dependent inhibition: crowded cells stop dividing, stop past one layer
  • This gives the currently existing cells a better chance to survive
• Anchorage dependence: cells must be attached to a substrate in order to divide
  • Ex: flat surface of neighboring cell or dish

Cancer cells exhibit neither density dependence or anchorage dependence.