Carcinogenesis Flashcards
(41 cards)
Types of DNA damage:
Single-strand breaks Double-strand break mismatch bases damage base intra-inter-strand crosslinks
Cause of pyrimidine dimers:
UV
Causes of single and double strand breaks
Strong radiation
Exogenous DNA damaging factors:
UV light
X-rays
Natural isotopes
Chemicals
Signature mutation of UV damage
CC to TT.
Bulky lesions
Mutation of alkylating agents
GC-AT transition. alkylated guanine can be mismatched with thymine
Major surveillance protein which looks for DNA damage =
ATM
Deficiency in ataxia-telangiectasia
Human autosomal recessive disorder.
Progressive neurodegeneration, cancer predisposition, premature aging
Endogenous p53 mutations usually located at what sites
CpG
CpG sites on p53=
Cytosine followed by guainine. Promoter regions that can be silenced when methylated
Mechanisms of mutation in CpG sites=
Not methylated cytosine may be spontaneously deaminated to uracil which can be repaired.
If cytosine has been methylated, it may be deaminated to to thymine (not repaired).
GC to AT transmission
Repair of alkylation damage:
Direct reversal
Molecule involved in direct reversal =
MGMT
MGMT
Suicide enzyme. DNA repair enzyme
Tumours with reduced MGMT expression are responsive to …
Treatment with alkylating agents
Enzymes involved in base excision repair =
DNA glycosylases
Endonuclease
Polymerase
Ligase
AP site
No base
Nucleoside excision repair is used when
- DNA glycosylases not recognisied
- bulky lesions (e.g. UV)
Ex of bulky lesion
UV CC to TT
Proteins involved in NER
XP proteins: Helicase Endonuclease Polymerase Ligase
Defect in nucleotide excision repair of UV damage which leads to increased sensitivity to sunlight
Xeroderma Pigmentosum
2 repair mechanisms for double strand break:
- Non-homologous end-joining
- Homologous recombination
Which kind of repair mechanisms maintains genetic info for double strand break
Homologous recombination
Non-homologous end-joining
Clean up ends, ligate back together
