Module 12
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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