Yapa Wijeratne

M/07/189

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 PO4

3- 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.)

Yapa Wijeratne

M/07/189

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starting the process of DNA replication after it has combined with S-cyclin. 2) S-cyclin is now destroyed & s-kinase is no longer active. 3) M-kinase is capable of turning on mitosis after it has combined with M-cyclin.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.

Yapa Wijeratne

M/07/189

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 Normal genes with normal function if gene mutate can be converted to Oncogenes

Yapa Wijeratne

M/07/189

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 P53 p53 production of protein can combine with 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