Wk 11: DNA damage + repair (Repair) Flashcards
What are the 5 types of DNA repair mechanisms?
- Base Excision Repair (BER)
- Nucleotide Excision Repair (NER)
- Mis-Match Repair (MMR)
- Non-Homologous End Joining (NHEJ)
- Homologous Recombination (HR)
What is base excision repair?
- DNA glycosylase excise faulty base
- 2nd strand serves as template
- AP endonuclease cuts backbone, AP lyase removes sugar
- DNA polymerase fills DNA gaps
- DNA ligase seals DNA
Is there a known defect to BER that is inherited?
No
What is BER used for?
Damaged base:
- 8-oxoguanine
- Deminated + dealkylated
Single strand breaks:
- Ionising radiation
What is Nucleotide excision repair used for?
Helix distorting DNA lesions:
- UV damage (remove pyrimidine dimers)
- Cisplatin cross links
- Bulky adducts
What is the inherited defect of NER?
Xeroderma pigmentosum:
- Autosomal recessive
- Mutation in XPA + XPC
- Sensitivity to light (skin cancer)
- Neurological impairment
What are the basic steps of BER + NER?
- Recognise damage
- Remove damage by excising part of 1 strand to leave gap
- Resynthesize to fill gap
- Use 2nd strand as template
- Ligate to restore DNA backbone
What is mismatch repair used for?
Catches damage not repaired by BER/NER
- Removes mis-paired nucleotides
- Deletions/insertions
- Repair DNA adduct from platinum based chemotherapeutic agents
What is involved in mismatch repair?
2 proteins:
- 1 detect mismatch
- 2 recruit endonuclease that cleaves newly synthesised DNA
What is non-homologous end joining used for?
- Double strand breaks
- Ionising radiation induced DNA damage
What is non-homologous end joining?
- ATM halts cell cycle
- Rapid repair mechanism
- Operates at all stages of cell cycle
- Error prone
What is the inherited defect of Non-homologous end joining?
Ataxia telangiectasia mutated gene:
- Autosomal recessive
- Neurological: ataxia (poor co-or) + telangiectasia (dilated blood vessels)
- Mutation: ATM
- Sensitive to ionising radiation + immunodeficient
What is homologous recombination repair?
- Error free
- Operates at S + G2 phase
- Requires sister chromatid
- BRCA 1 + 2 used to repair damaged DNA
What is the inherited defect of homologous recombination repair?
Breast cancer + ovarian cancer:
- Autosomal dominant
- Mutation: BRCA 1 + 2
Which cancer is associated with RB?
Retinoblastoma
