Module 12 Flashcards
Genome maintenance
What happens when gene maintenance go wrong
Cancer, deregulating cellular energetics, sustaining poliferative signalling, genome instability and mutation, replication immortality
What type of DNA damage can occur
chemical reaction
Spontaneous oxidative damage
hydrolytic attack (base is oxidise and removed, depruination)
uncontrolled methylation
What is an example of large disruptive lesion
Thymine dimers, hugely distorted by UV light, connecting two thymine together
Breaks in the DNA phosphate backbone
by ionising radiation, gamma ray
What error does polymerase pose
wrong base pairing, not base paired together properly(may end up with a permanent mutation.
What are the type of repair mechanism
Double strand break repair, nucleotide excision repair, single strand base excision repair, mismatch repair
What if lesion are not repaired
replication will stop and lose the whole strand.
What is a mutation
inheritable difference from the wildtype
Where must mutation be at for it to replicate
In the gametes or the cells that give rise to sperm and egg, or it need a large mutation for it to express it onto the nnext generation if it is else where(e.g skin cancer)
What is specific about mismatch repair
the method that is only specific to E. coli
What does mismatch repair do
methylation on the adenines in GATC sequence and hemimethylation on the new strand.
How to identify mismatch
using mut, cut the unmethylated side, exonuclease used to removed and polymerase to repair it.
What are the two similar repair systems
base excision repair(for small damage), nucleotide excision repair (for larger damage)
What is example of a damage to a single base
deamination, removed amine group and replaced with O, changed to uracil(from cytosine) or thymine (from 5-methylatedcytosine)
How to repair deamination
base excision repair, DNA glycosylase(uracil glycosylase if it is a uracil), then AP endonuclease to cut the backbone, DNA polymerase I will add the right base and use ligase to connect them
How to repair larger lerision
nucleotide excision repair, exonuclease cut 2 side, helicase used to hold them, DNA polymerase repair and ligase to close the nick
What causes double stranded break
Ionizing radiation, errors of DNA replication, oxidising agents, and other metabolites can cause breaks across both strands of the DNA
What is a error prone pathway or repair
repairs that contain large amount of errors (e.g double stranded break repair)
How does double stranded break repair
nonhomologous end joining, there are error because there are loss of nucleotide due to degration before end joining
What does G2 phase in cell cycle do
RNA and protein synthesis. No DNA synthesis
What does G1 phase in cell cycle do
RNA and protein synthesis, no DNA synthesis
What is G0 phase
terminally differentiated cells withdraw from cell cycle indefinitely and may resume at G1 to start
What controls the orderly process
Protein phosphorylation(inactivating and inactivating protein when phosphorylated), protein degration, protein synthesis, inhibitors(bind to protein to inhbit the protein)
What control cell cycle
kinase, all use the same way to regulate, cyclin
How is cyclin dependent kinases’s property
heavily regulated, stable protein levels across cell cycle, animals have 8 CDKs
What is cyclin
- Undergo a cycle of protein synthesis and degradation – protein levels are cyclical
- Essential regulators of CDK activity • Are also regulated
- Animals have 10 cyclins
- Can be divided into G1/S cyclins, S-cyclins and G2/M cyclins
What is mechanism 1 for regulating cell cycle
phosphorylation of CDKs, inactive, party active(active site is block) and fully active when it is bound to cyclin (allow target binding) Thr160 to activate and Tyr15 to inactivate (when phosphorylated)
What are the types of cyclins
E-CDK2(G1-S), cyclin A-CDK2(S-M), cyclin B-CDK1(G2-M), cyclin D is through out
Mechanism 2 for regulating the cell cycles
controlled degradation of cyclins, both tyr and thr are present, to allow it to activate quickly. positive regulate happens when phosphotase send signals then it will keep sending signal to produce for CDK(feebback loop). Negative feedback, binds to ubiquinine the more it activiate, to reduce it quickly.
What is destruction box recognization protein for(DBRP)
destruction box is a 9 amino acid sequence near the amino terminus. marked for degradation. Use proteasome to recycle the chain to amino acid.
Mechanism 3 for regulating the cell cycle
Regulated Synthesis of CDKs and cyclins
Mechanism 4 for regulating the cell cycle
Protein inhibitors of CDK activity
How does cyclin control them
by phosphorylating the target
Example target in mitosis
nuclear lamins(in nuclear), it phosphorylate lamins to allow nuclear lamina to decondense, causing chromosome to condense.
Condensin, to condense DNA when mixed together, known to no longer to condense when mutated in condensins, physically interacting with DNA
example of target in G1-S checkpoint control
Retinoblastoma(Rb), if there are damaged DNA are not repaired, it can pause the replication/mitosis or not completely replicated until it is repaired.
How does retinoblastoma work
Rb binds to E2F, CDK2 becomes active and phosphorylate pRb to stop it from inhibiting to allow replication if DNA is perfect
What is p53 for
cause inhibit p21 to be transcript when there is a break in the DNA. No longer be able to phosphorylate pRB, stop transcripting until the break is gone and p21 will degrade.
What is retinoblastoma disease
cancer forms in retinal cells in both eyes, not fatal, loss of vision, Rb was tumour suppressor gene clone.
What is sporadic cancer
cancer happen randomly, a cell with mutation and replicate until the pair of cell have both the mutation and it will produce a tumour.
What if gene can never be used to replicate anymore
Programmed cell death, p53, breaking down of the cell and be engulfed, apoptosis
What is the difference between necrosis and apoptosis
Necrosis is uncontrolled cell death that will burst open its content cause inflammatory response(too much errors). Apoptosis breakdown the contents inside and allow phagocytosis.
Uses of apoptosis
sculpting, metamorph, killing nerve cell to refine neural connection, destroy unwanted immunoreponse.
Why does tumour grow so fast,
They decreased in apoptosis, they dont die.
Function of telomeres
maintains length of chromosomes
What cell express telomerase
- Most human cells do not express telomerase because they do not need to divide
- Stem cells (cells to replenish other cells) express telomerase
- Germ cells (that produce gametes) express telomerase
What is senescence
terminal differentiation at approx 40-50 cell division, die if it divide further
What happen when telomere gets too low
Cell will undergo massive cell death
Difference of stem cells and somatic cells
stem cells contain telomerase to prevent degeneration, somatic cell dont not have telomerase
What happens telomerase reactivate
It will have unlimited cell replication
What is sunburn
radiation burn casing DNA damage triggers the production of melanin to protect further damage. if bad enough, it can trigger cell death pathways in the cell.
