CK L2 DNA Repair Flashcards
what is spontaneous deamination
the removal of an amino group from a molecule
DNA Replication Stress
Inefficient replication that leads to replication fork slowing, stalling and/or breakage
why is it imortant that spontaneous mismatches get repaired straight away?
because it will have a knock on effect during replication where a single mismatch will effect lots once its has been replicated
how can DNA replication stress occur?
if there is any machinery defects
why can lots of errors cause DNA replication stress?
because it causes delays which in turn causes stress
Types of DNA replication stress
> Replication machinery defects
Replication fork progression hindrance
defects in response pathways
how can repetitive DNA slow down DNA machinery and cause DNA replication stress
Repetitive DNA can lead to fork slippage
Fork slippage leads to…?
trinucleotide
trinucleotide repeat disorders
Huntingtons disease
trinucleotide repeat disorders- some info on Huntingtons disease
> CAG repeats > polylgutamine repeats > normal protein function still unknown Mutant protein aggregates in neurons > progressive, late onset disease
3 different outcomes of DNA damage response
> Senescence
Proliferation
Apoptosis
Senescence is…?
permanent cell cycle arrest
Apoptosis
Cell death
if DNA damage levels too high or persist what are the two outcomes
> Senescence
> Apoptosis
Proliferation…?
DNA repair
what do cell cycle checkpoints do?
slow dow the cell cycle to allows for DNA repair
the 4 steps in base excision repair
1) deamination converts one base into another e.g C into U (this is the error)
2) U is detected and removed leaving base-less nucleotide
3) Base-less nucleotide is removed leaving small hole in DNA backbone
4) The hole is filled with the right base by a DNA polymerase and the gap is sealed by ligase
what is a dimer
two identical subunits
4 steps of Nucleotide excision repair
1) UV radiation produces a thymine dimer
2) once the dimer has been detected the surrounding DNA is opened to form a bubble
3) enzymes cut the damaged DNA region out of the bubble
4) a DNA polymerase replaces the excised (cut-out) DNA and a ligase seals the backbone
4 steps of mismatch repair
1) a mismatch is detected in newly synthesised DNA e.g G paired with T.
2) the new DNA strand is cut and the mispaired nucleotide and its neighbours are removed by exonuclease activity
3) the missing patch is replaced with correct nucleotides by a DNA polymerase
4) a DNA ligase seals the gap in the DNA backbone
info on single strand breaks
> relatively simple
many diff mechanisms
integrity of DNA molecule intact
damage removed on one strand only
homology of other strand used to repair
not error-free but not error prone either
info in double strand breaks
> complex
integrity of DNA molecule lost
more likely to be error prone
use of homology may be possible
what are the two ways of repairing a double strand break?
1) non-homologous end joining
2) homologous directed repair
