Cell cycle, quiescence and senescence in eukaryotes Flashcards
What is free living cell growth regulated by?
Environmental cues such as nutrient supply.
What is cell growth and proliferation controlled by in multicellular animals?
Extracellular signals.
What is necrosis?
Unplanned death.
What is the cell division cycle?
The reproductive cycle of the individual eukaryotic cell.
What did Lee Hartwell discover?
Checkpoints.
What does necrosis occur in response to?
Damage or infection and can cause further damage to surrounding cells and tissues.
What did Tim Hunt discover?
Cyclin.
What did Paul Nurse prove?
That MPF was cyclic + Cdk, and he also isolated human Cdk.
What are four main phases of the cell division cycle?
Mitosis, growth/gap 1 and 2 and the synthesis phase.
What are the checkpoints in the cell cycle?
G1, S, G2, M.
What happens in the G1 checkpoint?
Checks for DNA damage and unfavourable extracellular environments.
What happens in the S checkpoint?
Checks for incomplete replication.
What happens in the G2 checkpoint?
Checks for insufficient cell growth.
What happens in the M checkpoint?
Chromosome incorrectly attached to mitotic spindle.
What are the checkpoints regulated by?
Cyclin/Cdk complexes.
What is Cdk?
Cyclin-dependent kinases.
How is the cycle taken from G2 to M?
M-phase promoting factor is activated from M-cyclin and M-Cdk working together with their regulators.
What causes a peak in Cdk activity?
A steady accumulation of cyclin followed by rapid destruction.
How is cyclin inactivated?
An inhibitory kinase (Wee1) phosphorylates cyclin.
What does activating phosphatase do?
It removes the inhibitory phosphates.
What happens after the activating phosphatase has removed the inhibitory phosphatases?
Active cyclin/Cdk phosphorylates Cdc25 (the activating phosphatase) - this is positive feedback.
What is the anaphase-promoting complex and what does it do?
It adds chains of ubiquitin molecules to cyclin proteins - tagging them for rapid destruction at proteosomes.
What happens if DNA is damaged at the G1/S checkpoint?
Protein kinases that phosphorylate p53 are activated. p53 binds to the regulatory region of the p21 gene and causes p21 protein to be formed - which is a Cdk inhibitor protein, causing S-Cdk cells to be inactivated.
What is the purpose of p53?
It allows time for the cell to repair damaged DNA or undergo apoptosis.
How may cancer form?
The p53 gene is mutated in at least 50% of human cancers - loss of its activity accelerates the accumulation of mutations required for uncontrolled proliferation of cancer cells - its molecular role as a transcription factor allows it to function genetically as a tumour suppressor.
What is G0?
When cells leave the cell cycle - undergoing apoptosis or entering a modified state called G0.
What differences occur in different cells in the cell cycle?
The time spent in G1.
What are Quiescent cells?
Cells that have withdrawn from G0 but have the capacity to re-enter the cell cycle when appropriate.
What allows quiescent cells to exist?
The regulation of the G1/S phase checkpoint by retinoblastoma (Rb) protein.
What are Retinoblastoma sequester transcription factors important for?
Initiating DNA replication and nucleotide metabolism at the start of S phase.
How is the Rb transcription regulator activated?
Mitogen binds to a receptor that activated G1-Cdk and G1/S-Cdk which phosphorylates Rb which promotes the release of transcription factors that promote the initiation of S phase - transcription, translation and resulting cell proliferation.
What do mitogen signals promote?
Cyclin synthesis and KIP degradation.
What are examples of terminally differentiated cells?
Neurons, keratinocytes in the skin, goblet (secretory) and enterocytes (absorptive), gut epithelial cells.
What does it mean that cancer cells are immortalised or transformed?
They evade senescence and can continue dividing.
What is cellular/replicative senescence?
When cells lose the capacity to divide - this is a post-mitotic state.
What are contributing factors to cellular/replicative senescence?
The accumulation of KIP/CIPs with successive divisions and the shortening of telomeres.
What is cell number a balance between?
Cell proliferation and apoptosis.
What is the aim of apoptosis?
Remove unwanted cells in an organised way, such as webbing between digits during animal development.
What happens if there is excess neurons?
Cell death will match the number of nerve cells to the number of target cells.
What are telomeres?
Repetitive sequences at the ends of chromosomes.
What are the two biological problems that telomeres create?
Free chromosome ends could stimulate the DNA-damage response pathway and the ends of chromosomes cannot be replicated by normal DNA replication.
How can some cells overcome senescence?
Activating telomerase reverse transcriptase or acquiring mutations that release blocks on the cell cycle, such as mutations in p53 or Rb.
Why does the last part of the 3’ end of the chromosome get shorter through every replication?
An RNA primer is needed to replicate DNA strands, but a primer cannot be placed beyond the very end of the chromosome.
What happens when the 3’ end (telomeres) gets shorter below a certain threshold?
The exposed DNA is recognised as a DNA double-strand break (DSB) by the DNA damage response (DDR) machinery. This triggers the DNA damage checkpoint and this is the basis of replicative senescence.
How can the ends of chromosomes be extended?
Telomerase.
How does telomerase work?
It adds additional repeats to the telomerase template strand, and the lagging strand is completed by DNA polymerase.
What does telomerase reverse transcriptase do?
It makes DNA from RNA.
