DNA Repair and Cancer Flashcards
What kinds of damages are there to DNA? Which is worse?
Single stranded damage
Double stranded damage. This is worse.
What are some exogenous sources to DNA damage?
Ionising radiation Alkylating agents Mutagenic chemicals Anti-cancer drugs Free radicals
What are some endogenous sources to DNA damage?
Replication errors
Free radicals
Give some types of DNA damage that can happen.
Apurinic site Deamination Mismatches Doublestrand breaks Intercalating agent Single strand breaks.
What is deamination?
When G pairs up with U instead of C for example. (Involving Uracil)
What is mismatching?
When G pairs up with T instead of C for example.
How can mismatching be fixed?
By proofreading. When a mismatch occur DNA exonuclease can come in and remove the mismatched nitrogenous base to then start again.
Why can repetitive DNA be a problem?
It can lead to fork slippage. When a sequence is repeated CAGCAGCAGCAGCAG over and over again a lot of complementary nucleotides want to match it. This results in the new strand having either an extra nucleotide or one too few. (Insertion and deletion)
What are trinucleotide repeat disorders?
Where fork slippage has occurred and either insertion or deletion occurred. Such disorders as Huntington’s, Spinocerebellar ataxia and Fragile X.
Explain Huntingtons on a MCBG level.
A lot of CAG repeats. Insertion mutation occurs and whereas a normal gene should have 6-39 repeats the Huntington one has 35-121 repeats.
This means that the protein coded for (Huntingtin) does not fold normally and aggregates in nerves.
Explain replication stress.
Inefficient replication that leads to fork slowing, stalling and/or breakage.
What are the three outcomes in case of DNA damage in response pathways?
Senescence
Proliferation
Apoptosis
What is senescence?
When a cell can’t divide anymore but still carry out its function.
It can pick up more mutations and more dangerous mutations in the long run.
This also causes permanent cell cycle arrest.
What is proliferation?
When the cell continues to divide with its mutation.
This is actually the preferred outcome due to DNA repair.
What is apoptosis?
When the cell dies instead.
How does base excision repair work?
Deamination occur which converts a cytosine base into a uracil.
The uracil is detected and then removed by exonuclease leaving a base-less nucleotide.
The base-less nucleotide is removed leaving a small hole in the DNA backbone.
The hole is then filled with the right base by DNA polymerase and the gap is sealed by ligase.
How does nucleotide excision repair work?
UV radiation produces a thymine dimer. This causes to thymine to link together on the same strand and creates a ‘bubble’.
When the dimer has been detected the surrounding DNA is opened to form an even larger bubble.
Exonuclease then cut the damaged region.
DNA polymerase replaces the excised DNA and ligase seals the backbone with new DNA.
How can double strand breaks be repaired? What is most favourable?
By non-homologous ends joining.
By homologous ends joining. This is most favourable. Ideally it is two sister chromatids.
Explain non-homologous ends joining.
DNA-PK removes damaged ends.
Ligase joins two non-homologous ends together.
This is likely to form mutations.
What are the different steps of cancer?
Normal cell Hyperproliferation Early adenoma Intermediate adenoma Late adenoma Carcinoma Metastasis (In between these steps several mutations need to happen.)
What are heterogenous tumours? Why can they be extra dangerous?
Tumours which are not of identical cells. Because this means that some parts of the tumour might be resistant to different drugs. Meaning one drug might not work on all of the tumour.
