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DNA Damage - Coggle Diagram

- - - - Transition is purine-> different purine or pyramidine-> different pyramdine
      - Transversion is purine -> pyramidine or vice versa
      - The number of possible transversions is double possible transitions but transitions arise more frequently
  - - - mutation where number of copies of nucleotides increases in succeeding generations
      - first discovered in FMR-1 gene- wildtype has 54 or fewer copies of CGG whereas mutation can have hundreds-thousands of repeats
      - Huntigton disease- toxic protein produced with extra glutamine because of CAG repeats
      - this mutation also appeats to be related to secondary structures that interfere with replication; it can also affect expression by causing DNA to be methylated
  - - - Intragenic
        
        takes place in same gene as original mutation
        
        may change second nucleotide in same codon or may work by supressing a frameshift mutation
        
        can also make compensatory changes to folding by recreating the original folding pattern changed by the first mutation
      - Intergenic
        
        occurs in gene other than original mutation
        
        can work by changing the way RNA is translated (for example preventing a nonsense mutation by mutating tRNA so that it can bind to the new stop codon (example- tRNA anticodon mutation of AUA to AUC so it binds to UAG (stop) codon which then adds tyrosine)
        
        can work through gene interaction so that polypeptide chains from 2 genes interact to produce a functional protein so suppressor mutation may produce compensatory change that restore interaction
- - - - Catalases (Kats)
      - Peroxidases (alkyl hydroperoxide reductase)
      - superoxide dismutases
  - - - hydroxyl radicals generate damaged bases
      - can produce clustered lesion and causes chain breaks
    - - particle imparts its energy directly to the DNA, this can break sugar phosphate backbone
      - UV
        
        UV-B results in fusion of adjacent pyrimidines in DNA
        
        Cyclobutane pyrimidine dimers and 6-4 photoproducts are the main products
        
        the adjacent lesions are fused which interferes with base pairing and is bulky so distorts the helix can block replication, most are immediately repairs
        
        Outcomes
        
        5'-methylcytosine never forms 6-4 lesions
        
        TC(6-4) and CC(6-4) are common
        
        TT(6-4) are less common and CT(6-4) never forms
        
        has less energy than ionising radiation and does not dislodge electrons ut pyrimidine bases absorb the light to create pyrimidine dimers by forming bonds between pyrimidine on same strand
        
        Thymine dimers are most common, but cytosine and thymine-cytosine can occur
        
        Bacteria have SOS system which circumvent replication blocks but also akes numerous mistakes
  - - - adds methyl or ethyl groups to bases' aromatic ring
      - addition to aromatic ring can alter pairing properties and are called miscoding lesions
      - G-> 0-6 Ethylguanine which pairs with T
      - can block replication
      - ethylmethylsulfonate adds ethyl to G producing O6-ethylguanine which pairs with T and can also add ethyl group to T producing 4-ethylthymine which pairs wtih G
    - - Benzo(a)pyrene is metabolized to an epoxide that acts on the N2 group of G
    - - chemical similar to standard nitrogen base so polymerases cannot distinguish from standard bases
      - 5-bromouracil (5BU) is thymine analog (same but bromine instead of methyl), normally bases with A but can pair with G
      - 2-aminopurine (2AP) is anolog of adenine, so can pair with T but also with C
    - - nitrous acid deaminates C creating U, also changes A into hypoxanthine which pairs C, also deaminates G producing xanthine which pairs C and T
    - - adds hydrocul group to C converting it to hydroxylaminocytosine, this transition increases rate of a tautomer that pairs with A instead of G
      - since only acts on C it cannot reverse its own mutations
    - - Radicals are produced in aerobic metabolism and by radiation and certain drugs
      - the reactive forms inuce mutations by changing DNA
      - oxidation converts G into 8-oxy-7,8-dihydrodeoxyguanine which mispairs with A
    - - Proflavin, acridine orange, ethidium bromide and dioxin are examples
      - they produce mutations by intercalating themselves inbetween bases in DNA distorting the duplex and causing insertions adn deletions in replications
      - produce insertions and deletions so can reverse mutations
- - - - deamination of C into U which pairs with A, which then pairs with T
      - in mammals some C are naturally methylated to 5-methylcytosine (5mC) and when 5mC is deaminated it becomes T
- - - - short flanking repeats of 3-12bp on both sides of the transposable element which are not part of the element but are generated in the process of transposition at the point of insertion; flanking repeats are created when staggered cuts are made in DNA
      - Some transposable elements end with terminal inverted repeats of 9-40bp in length and are recognised by enzymes that catalyse transposition
  - - - DNA transposons
      - retrotransposons- tranpose through an RNA intermediate (uses replicative only)
      - replicative transposition- new copy is introduced at a new site while old copy reminas at original site
      - non-replicative transposition- transposable element is removed from old siteadn inserted at new site
    - - DNA methylation suppresses transcription by preventing production of enzymes
      - altering chromatin can prevent transcription of transposon