1. Yapa Wijeratne
Cell Cycle
RBC ---> x No nucleus.
Nerve cells ---> G0-G1 (permanent)
Liver
Potential G0-G1 (not permanent)
Turnover
Repair
Contact inhibition (packing of cells tightly)-prevents cell division cycle in liver. Adhesion
Intestinal epithelium-enterocytes (2-5 days)
Bacteria, yeast -20 min
Volume=k
t
If the volume is constant, even with the presence of sugar due to spatial inhibition increase of
number of cells moderates.
Cell division cycle
M
Start point/restriction point
G1-Gap 1 phase
Collect nucleus
Cell grows in size & cellular organelles begin to double in number.
S-Synthetic phase-Replication DNA.
G2-Gap 2 phase
Checking the correctness of synthesis of DNA.
Collect any nucleic/ material.
Synthesis of proteins.
M-Mitotic phase
Check points-monitored by Group of proteins- Cyclins, CDKs-Cyclin Dependant protein Kinases
Kinases-is an enzyme that removes a PO43- group from ATP & adds it to another protein. The
phosphorylated molecule, which may also be a kinase, is not activated.
Kinase involve in cell cycle Cyclin dependant
Because they are activated when they combine with protein-cyclin.
Cyclin-
o Because their quantity is not certain. They increase & decrease during cell cycle.
o They increase in amount until they combine with a kinase.
o This is a suicidal act.(Kinase activates various enzymes. One of which destroys the cyclin.)
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2. Yapa Wijeratne
Cyclin level
t
1) S-kinase is capable of starting the process of DNA replication after it has combined with S-cyclin.
2) S-cyclin is now destroyed & s-kinase is no longer active.
3) M-kinase is capable of turning on mitosis after it has combined with M-cyclin. This starts the
process of:
i) Chromosome condensation
ii) Nuclear envelope breakdown
iii) Spindle assembly
4) Now M-cyclin is destroyed.
Phosphorylation of protein kinases of specific seryl, threonyl or tyrosyl residues regulates many
human enzymes.
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3. Yapa Wijeratne
Cytoplasm contains Protein serine kinase, Protein threonine kinase
Regulation of metabolic activities -Phosphorylated for glycogen synthesis, cell cycle, signal
transduction .
Glucose Glucokinase/Hexokinase Phosphorylation
Phosphorylation of enzymes may or may not increase the active state of its original state. Same way
it may or may not activate the original state of dephosphorylated substance. So this action act as a
switch.- Reciprocal regulation
Substance-OH P
Dephophorylated substance
Growth Factors
Some factor is needed to signal for cell division in tissues. Growth factors attach to receptors in cell
membrane. They signal cell division.
e.g.
o EGF-Epidermal Growth Factor-Stimulates growth of many epidermal & epithelial cells.
o Growth factor cell cyclin1 + CDKs P1 P2 DNA cyclin2 + CDKs P3 ….
o Pygmies produce GH but their plasma mem. receptors are faulty & cannot contact with GH.
Transcription factors-affects in cell division
o Synthesis RNA from DNA
o Replication DNA from DNA
MPF-Maturation Promoting Factor acts in G1 –Restriction Point
When there is a Growth factor cyclin+Kinase cell division
NO Growth factors cyclin(has gone awry)+Kinase (which is not required) cell division would be tumor
Oncogenes
Code for cyclin(has gone awry) Uncontrolled cell division Cancer
Proto- Oncogenes
if gene mutate can be converted to
Normal genes with normal function Oncogenes
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4. Yapa Wijeratne
Tumor Suppressor Gene
e.g.
RB1-involved in genesis of Retinoblastoma
Small cell lung cancers
adenocarcinomas of the prostate inactivated by RB1
tumors originating from retina, bone & connective tissue
RB1 Rb Cell cycle regulator-it binds to & inactivates a transcription factor necessary for the
transcription of certain genes(progression from G1 > S phase)-histone genes, DNA replication genes.
P53—Guardian of the genome
can combine with
P53 p53 production of protein cyclin-kinase complex
Prevents from becoming active/inhibitor
o p53 acts as a transcriptional regulator, presumably regulating certain genes that participate
in cell cycle.
o The level of p53 increases after exposure to agents that damage DNA. This causes G1 specific
cell cycle arrest & allows time to DNA repair to occur. It also triggers apoptosis, so that
damaged cells die.-Guardian of genome
o p53 is not required for normal cell development, but its absence greatly increases the
occurrences of tumors and is associated with genome instability.
If,
 DNA damage is detected either the G1 or the G2 phase.
 Genome is incompletely replicated.
 Normal chromosome segregation machinery is incomplete(i.e. defective Spindle)
Cell will not progress through the phase-where defects are affected
If damage cannot be repaired.
p53
Activate coll. Of key genes be a component of repress genes necessary for cell
Induce apoptosis biochem. Series of events survival
result in Apoptosis
APOPTOSIS
Programmed cell death
High level of radiation
DNA-active chemotherapeutic agents
Cells lacking p53 NO Apoptosis
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