DNA Repair And Cell Cycle Flashcards
Cell cycle- g1 phase
Cell content duplication
10-12 hours
S phase
DNA replication.
6-8 hours
G2 phase
3-4 hours
Double check and repair
M phase
Less than an hour
Mitosis
What are the exogenous sources of DNA damage
Ionising radiation UV Alkylating got agents Mutagenic chemicals Anti-cancer drugs Free radicals
What is dna replication stress
Inefficient replication that leads to replication fork slowing, stalling and or breaks
How does DNA polymerase deal with misincorporation
DNA polymerase can sense it has replicated wrong therefore reverses so it can remove the wrong base and put the right one in- proofreading
What does fork slippage lead to
Trinucleotide expansion
Huntington’s, spinocerebellar ataxia, fragile X
What is senescence
Permanent cell cycle arrest
Wont divide anymore no function
Base excision repair
Used when there is the wrong base
- deamination changes base
- wrong base identified and removed leaving a base less nucleotide
- base-less nucleotide removed leaving a small hole in the DNA backbone
- hole is filled with the right base by DNA polymerase and gap is sealed by DNA ligase
Nucleotide excision repair
- UV radiation produces a dimer
- once the dimer is detected the surrounding DNA is opened to form a bubble
- enzymes cut the damaged region out
- a DNA polymerase replaced the excised DNA and ligase seals the backbone
Mismatch repair
- mismatch is detected in newly synthesised DNA
- new DNA strand is cut and the misread nucleotide and its neighbours are removed by exonuclease activity
- missing patch is replaced with correct nucleotides by a DNA polymerase
- a DNA ligase seals the gap in the DNA backbone
Non homologous end joining
Broken ends recognised and protected
Complex formed and damaged ends removed
Broken ends ligated
Error prone
What determines the type of DNA double strand break repair that occurs
The stage of the cell cycle that the cell is
Homologous directed repair
Firstly, the exposed ends of DNA are resected.
This mechanism utilises a homologous template – which essentially means an undamaged copy of the DNA involved in the double-strand break – e.g. a sister chromatid.
A Holliday Junction then forms between the broken DNA and the DNA template.
The Holliday Junction is then nicked complete the repair.
What is clonal expansion
Different clones in 1 tumour
What negative effects can chemotherapy have on tumours
Clones of cells in a tumour have differential sensitivity to the chemo- the chemo may work on one cone but nit another so that one will continue to grow- shows why tumours shrink then grow back
Chemotherapy-induced mutagenesis- by trying to kill the clone you can mutate them even more making them more resistant to chemotherapy
What are synthetic lethality strategies
If we know that a certain gene doesn’t work to keep the cell alive we can ensure that the only pathway the cell can take i that pathway which would kill the cancer cell by giving treatment that promotes that pathway
What are some endogenous causes of mutation in DNA?
DNA replication errors
Free radicals