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Lecture 20

BIOL 3113 Lecture Notes - Lecture 20: Growth Factor, Mitosis, Cytokinesis


Department
BIOL
Course Code
BIOL 3113
Professor
Barbara S
Lecture
20

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20 Cell Cycle Control System
The cell cycle - orderly sequence of events by which a cell duplicates its contents and
divides into two
How cell coordinates various steps of its reproductive cycle?
Cell-cycle control system - network of regulatory proteins that governs progression of a
eucaryotic cell through the cell cycle
Cell-cycle control system - responds to various signals from inside (monitoring of the
progression through cell cycle) and outside the cell (monitoring of the conditions in cell
environment)
The cell cycle control system consists of a series of biochemical checkpoints at which the
cycle arrests until certain conditions are met and/or certain external signals are received
Eucaryotic cell cycle - 4 phases
*M phase (mitosis + cytokinesis)
*S phase
*G1 phase
*G2 phase
S + G1 + G2 = Interphase
Duration of the cell cycle varies greatly from one cell type to another (from minutes to
years)
The cell cycle control system - Series of biochemical checkpoints
Most important: G1 and G2
G1 checkpoint
Principal checkpoint
Sometimes referred to as "Start"
Most interphase cells are arrested at this point
Passage through this point triggers entry into the S phase
*Conditions and signals:
Cell size: Is the cell big enough?
Environment: Are environmental conditions favorable for division?
DNA: Is the DNA damaged?
Growth factors: Are appropriate external signals present?

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G2 checkpoint
Controls entry into mitosis
Passage through this point triggers entry into the M phase
Conditions and signals:
Cell size: Is the cell big enough?
DNA: Is all of the DNA replicated?
External Signals - Growth Factors
Growth Factors are external signals that act at the checkpoints to affect the cell cycle in
one of two ways:
Promote cell proliferation
Inhibit cell proliferation
Mechanism of Cell Cycle Control
The cell cycle is controlled by cycles of activation (by phosphorylation) and inactivation
(by dephosphorylation) of key control proteins:
*The enzymatic reactions are mediated by a specific set of protein kinases and protein
phosphatases
*The activities of these enzymes rise and fall cyclically, in synchrony with the cell cycle
*Enzyme activity controlled by cyclins
control proteins
not enzymes
concentration rises and falls in a cyclical manner
responsible for cyclical activity of enzymes
Enzymes controlled by cyclins are called cyclin-dependent protein kinases (Cdks), e.g.,
M-Cdk
relatively constant concentration
activity varies depending on the concentration of the appropriate cyclin e.g., M-cyclin -
helps drive cells into M phase
Concentration of cyclins rises gradually during the cell cycle and their rapid elimination
initiates the exit from one phase and progression to the next
Example: M-cyclin (acts in G2 to trigger entry into M phase)
synthesis starts immediately after cell division and continues at the steady level during
interphase - accumulation - the highest level just before mitosis
sudden fall in M-cyclin concentration toward the end of mitosis due to rapid M-cyclin
ubiquitination and destruction in proteasomes
destruction of M-cyclin inactivates M-Cdk
Activation of M-cyclin-Cdk complex
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