Flashcards in Cell Cycle, Proliferation, Apoptosis Deck (28)
What happens during G1?
Cell growth and contents duplication.
What are the two main classes of regulatory molecules in G1?
Cyclins and cyclin-dependant kinases.
Describe the biochemical pathway that leads to G1/S transition.
Cyclin D produced
Cyclin D binds to CDK4
Cyclin E gene transcribed
Cyclin E binds to CDK2
CyclinE-CDK complex prepares cells for G1/S transition
Increase in factors that promote S phase cyclin and DNA synthesis
Decrease in molecule inhibiting S phase
What happens during S?
DNA replication, synthesis of DNA proteins, chromosome formation, joined by centromeres.
How is the S phase controlled?
Active S cyclin-CDK complexes phosphorylate proteins that make up the pre-replication complexes on DNA replication origins. One complex at each origin for one replication only.
What happens during G2?
Preparation for Mitosis.
During what stage of the cycle is DNA condensation most extreme and a karyotype is obtained?
What happens in late prophase?
Nuclear envelope disappears
Spindle apparatus forms in the cytoplasm.
During what stage of the mitosis does spindles attach to centromeres?
What are the major molecules that regulate the cell cycle?
Rb, p53 and CDK to some extent.
What is the function of Rb?
In its dephosphorylated state it prevents entry into S phase
What is the effect of Rb phosphorylation?
Inactivation of Rb and S phase.
What disease results from homozygous Rb mutation?
Retinoblastoma and 6x increased risk for other cancers.
Is retinoblastoma recessive or dominant?
Recessive (need to be homozygous for disorder).
What is retinoblastoma?
Tumour in retina
What is the function of p53?
Activates transcription of inhibitors of the CDK/cyclin kinases to block G1/S transition. Critical apoptosis component.
What percentage of tumours contain a p53 mutation?
p53 can start or contribute to cancers.
Name a gene critical for apoptosis.
What intracellular signals can lead to apoptosis?
DNA damage, changes in intracellular calcium.
List the 6 steps of apoptosis.
Cytoplasm density increases
Apoptotic body formation.
Describe step 1 of apoptosis.
Cell shrinkage and rounding occurs through caspase-mediated breakdown of the cytoskeleton.
Describe step 2 of apoptosis.
Cytoplasmic density increases, tight packing of organelles.
Describe step 3 of apoptosis.
Pyknosis: condensation and localisation chromatin to the nuclear envelope.
Describe step 4 of apoptosis.
Karyorrhexis: DNA in the nuclear envelope is fragmented and the nuclear membrane is broken down.
Describe step 5 of apoptosis.
Blebbing of the cell membrane.
Describe step 6 of apoptosis.
Cell is broken down into apoptotic bodies, which are phagocytosed.
How can one determine if the rate of apoptosis is high?
Run PCR of produced DNA fragments.