DNA repair Flashcards
How does DNA get damaged - endogenous sources ?
Replicative errors
oxifative damage by free radiscals
spontaneous alteration e.g. base loss
alkylating agents ( bi producted of reactions) can modify DNA
Exogenous sources of dna damage
uv
pollution
carcinogens
radiotherapy - cause breaks in DNA
chemotherapy - tend to cause base modification and crosslinks
what sort of changes occur ?
intrastrand crosslink - two bases on same strand become covalently attatched
strand break - either single or double
pyrimidin dimer - a type of intrastrand crosslink
base change
base loss
interstrand crosslinks
base modification
bulky adduct- large chmeical structure added to base causes distortion
protein cross link - protein covalently linked to DNA
DIrect reversal explain
enzyme removes linkage between bases-photolyase
works for multiple pathways
Nucleotide excision repair - NER explain?
the error is removed as a stretch of nucleotides.
enzymes make cuts around damage and gap is filled with polymerase
two types - general
transcription coupled - only for transcriptional regions
Base excision repair
only affected base is removed
dna glycosylase makes encision
another molecule removes base
polymerase fills gap
Mismatch repair
similar to nucleotide excision repair but removes mismatched base and not modified
detects error - mismatch protein binds to error and finds a nick in strand and removes the whole strand .
only during replication
proteins- Mut proteins(MutS/H/L)
Strand invasion
Dna strand from broken double helix invades another double helix
Homologous recombination - Double strand break repair`
only in S phase when chromosome are present
DSB - enzyme chew back arms to leave overhanging single stranded ends
one invades other and forms cross over and then is extended
second end capture - remaing strand also invades other strand and causes two cross over points and then resolution where nucleases cut the points and rejoin strands
Homologous recombination - strand displacement, strand anealing
SDSA is preffered in mitosis - occurs s/g2
similar to DSBR one strand invades intact sister uplex but second strand part dont happen that inital strand is copeid of its own structure and strand displacement annealing happens generating a non crosobver
Homologous recombination - single strand anealing
only occurs when there are adjacent repeats
always loose one of the repeats
DSB happens - resection happens until repeat is found
annealing happens and chew back of displaced strand
then trimmining and filling in
Homologous recombination - Break induce replication
only occurs when there in 1 end with homolgy e.g. during DNA replication ahead of the fork of s phase.
resection of strand happens than strand invasion but sister chromosome is used for the rest of replication
Micro homolgy mediated end joining
during S phase
dna ends dont look for complete homology but short sections and when found it joins rejoin that shows homology and trims away extra dna and fills in gap - mutagenic
NON homologous end joining
dSBs are repaired by randomly fusing them -early s and G0/1
ku binds to two end and joins them together randomly
Trans lesion synthesis
when cell encounter problem in replication it can either bypass or wait for repair . leaving it on lagging strand is find due to okasaki fragments but not on leading.
syntehsis past leasion by trans lesion polymerases - most have high error rates
template switching - leading strand synthesise up to lesion and lagging strand past lesion results in one of two structures chicken foot or normal recomb structure.
leading strand is replicated of lagging strand and will bypass lesion.
