DNA damage and repair Flashcards
1
Q
How does DNA get damaged - endogenous sources
A
- replicative errors - incorrect base insertion, insertion, deletions
- oxidative damage by free radicals
- spontaneous alteration in DNA
- akylating agents (malondialdehyde )
2
Q
How does DNA get damaged - exogenous sources
A
- UV
- pollution
- carcinogens smoking
- radiotherapy - x-ray
- chemotherapy - alkylating agents, cisplatin, mitomycin C
3
Q
What sort of changes occur?
A
- intrastrand crosslink - two bases on opposite strands become covalently attached
- strand break
- pyrimidine dimers - intrastrand crosslink
- base change
- bass loss
- interstrand cross-link
- base modification
4
Q
How are the errors dealt with?
A
- direct reversals - multiple specific pathways
- nucleotide excision repair (NER)
- base excision repair (BER)
- mismatch repair
- homologous replication (HR)
- break induced replication (BIR)
5
Q
Describe direct reversals
A
- reverses chemical process which has occurred
- eg reverses methylation - by removing methyl group
6
Q
Describe NER
A
- error is removed as a stretch of nucleotides
- enzymes recognise damage and make cuts in damaged area, whole area is removed and gap is filled using polymerase
7
Q
Describe BER
A
- only the affected base is removed
- DNA glycosylase makes excision and AP endonuclease removes base
- filled with DNA polymerase and DNA ligase
8
Q
Describe mismatch repair
A
- similar to NER, but not removing a modified base just removing base in wrong position
- protein group involved = Mut protein (MutS, MutH, MutL)
9
Q
Describe strand invasion
A
- a DNA strand from a broken double helix invades another double helix
10
Q
Describe HR - double strand break repair (DSBR)
A
- only occurs in S phase when homologous chromosomes are present, so late S/G2
11
Q
Describe HR - strand displacement strand annealing SDSA
A
- preferred in mitosis - late S/G2
- many proteins - MPH1, SRS2
12
Q
Describe HR - single strand annealing SSA
A
- only occurs when there are adjacent repeats, always lose one of the repeats
- many proteins - Rad52, Rad1, Rad10
13
Q
Describe HR - break induced replication BIR
A
- only occurs when there is only 1 end with homology eg during DNA replication ahead of the fork or outside of S phase
- also some role at telomeres if telomere is absent
- can be used for replication restart at collapsed replication forks
14
Q
Describe HR - micro homology mediated end joining
A
- occurs through S phase
- main proteins - Ku, DNA-PK,
15
Q
Describe non-homologous end joining NHEJ
A
- double strand breaks DNA are repaired by randomly fusing them usually occurs early S before replication
- find two DNA ends, protein brings ends together
- DNA ligase joins them
- proteins involved - Ku, DNA-PK
