Lecture 13 Flashcards
list some extrinsic mutagens.
- uv
- ionizing radiation
- chemicals
- cooking/smoking
- food carcinogens
list some intrinsic mutagens.
- heat (deamination, depurination)
describe the ames test.
so Salmonella HIS- cannot proliferate on an agar plate without Histidine provided. However, if there is reversion mutation to HIS+, then they can proliferate on an agar lacking histidine. This test is used to measure the mutagenic properties of a substance.
what is the most common DNA damage?
depurination with 10,000 events per cell per day
what are the three major types of DNA damage repair?
1) excision repair (cuts dna)
2) Non-excisive repair (no cutting of DNA, direct repair)
3) DNA double-stranded break repair
what are some preventative measures for DNA damage?
- detoxification of oxygen radicals and alkylating agents
- hydrolysis of damaged dNTPs to prevent incorporation into DNA sequence
what are the steps of excision repair?
- repair endonuclease comes in and removes damaged dna
- dna polymerase fills in the gap
- dna ligase seals new dna into surround dna
difference betwen nucleotide excision repair and base excision repair?
- for NER, first step is strand cleavage and the gap is usually 12-30 nucleotides long
- for BER, first step is glycosyl bond cleavage and the gap is usually less than 10 nucleotides (typically 1-2)
what are the characteristics Xeroderma pigmentosum?
there is a defect in nucleotide excision repair so there is hypermutagenesis
what are the characteristics of Cockayne Syndrome?
photosensitivity, growth and mental retardation, premature aging, very little skin cancer
what are the characteristics of Trichothiodystrophy (TTD)?
mental and growth retardation, britlle hair and nails due to sulfur deficiency, UV sensitivity, no cancer predisposition
what are the characteristics of Bloom Syndrome?
growth defects, sun sensitivity, skin pigmentation, chromosomal instability, male infertility, cancer predisposition
- defect in recombination, including DSB repair
what are the characteristics of Werner Syndrome?
cancer predisposition, premature ageing, chromosomal instability
- defect in recombination, including DSB repair
what is p53’s role in dealing with DNA damage?
1) for moderate dna damage - activate p21 which then causes the cell cycle to stop and allows for DNA repair
2) for extreme dna damage - apoptosis via Bax/Fas