Spontaneous and induced mutations.txt

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Spontaneous and induced mutations.txt
2012-04-28 13:25:55
spontaneous external mutations

external (induced) and spontaneous mutations
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  1. Spontaneous Mutations
    • Depurination most common type of naturally occurring chem. Change
    • Thru reaction with WATER, can remove A or G from DNA, leaving sugar-phosphate backbone intact.
    • Generally recognized by DNA repair enzymes, to assist in 10,000 purines lost every 20hrs at 37degrees per cell.
  2. Base loss through depurination
    • During replication: if not repaired, newly synthesized strand will INSERT a random nucleotide (as there is no template for complementary base at apurinic site), usually A
    • As the next round of replication starts, the newly synthesized strand will now have A, which will then be complementary replicated w/T, which will lead to permanent mutation.
  3. Role of mutations in aging germ cells and brain cells
    • PATERNAL Age Effect:
    • Spermatogenesis is a CONTINUOUS process from puberty til death
    • Inefficiency of DNA repair pathways
    • In mouse exp. The cells with higher the rate of replication and division showed INCREASE mutagenesis.
    • Also showed that as more DNA damage occurred (with older mice) there was LESS DNA amplification
  4. Mutations in Intestines related to aging:
    • With duodenum: mutation FREQUENCY Increased w/age
    • With Duodenum and jejunum: MORE mutation in MUCOSAL vs. serosal layers (ileum showed no change b/w the 2)
  5. External Mutations
    • Common UV radiation mechanism
    • Mostly involves UVB photons being ABSORBED by DNA bases (mostly pyrimidines)
    • Thymine cyclobutane dimer forms
    • 2 or more unsaturated molecules combine to form CYCLIC adduct, causing reduction in bond multiplying.
  6. Effects of UV radiation on DNA
    • UVB being absorbed causes thymine dimers to form, causing SUNBURN and production of MELANIN
    • INDIRECT DNA damage occurs through chromophore forming Free Radicals (NON-Sunburn..so NO warning sign or pain)
  7. Formation of free radicals
    • UV light can be absorbed by CHROMOPHORE
    • Chromophore is now EXCITED
    • Reactions occur b/w this chromophore and DNA to Produce FREE Radicals
    • Free radicals can be the addition of an OH group through OXIDATION, or add’n of OXYGEN singlet (O2)
  8. Enzymes that STOP free radicals
    • Superoxide dismutase: converts Superoxide back into diatomic oxygen
    • Catalayse: converts H2O2 to>> O2 and H20
    • Glutothione peroxidase: H202 to >> O2
    • Vitamin C & E and melatonin: good defense for FREE radicals, but NO Enzyme against it, it’s too fast and small
    • Lycopene is good to take (tomato paste) as well
  9. Polycyclic Aromatic Hydrocarbons (PAHs):
    • Carcinogenic and form from incomplete combustion organic materials
    • Can BIND to DNA
    • Most potent is BENZO(a)PYRENE
  10. Binding of PAHs with DNA
    • Large aromatic bound structures IMPEDE DNA replication and disturb normal FXN
    • Add’n of BP distorts angle of DNA, causing a LOSS of hydrogen bonds
    • 2 BP conformations possible: Cys and Trans
    • Cis: Intercalated and MORE energenetically STABLE, therefore more detrimental to replication (frameshifts, loss of H+, structure changes)
    • Trans: Binds to MINOR groove of DNA, where it ALLOWS for DNA replication to occur
  11. p53:
    • Tumor SUPPRESSING protein: prevents cells from DIVIDING inappropriately
    • Deficiency in this can lead to tumor growth
    • 50% of cancers known to have mutations in p53