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Regulation of Gene Expression in Bacteria and Their Viruses

Regulation of Gene Expression in Bacteria and Their Viruses...

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Gene Mutations Tautomeric Shifts – one tautomer into another, usually a keto (normal base) with the wrong imino or enol base Spontaneous Lesions – naturally occurring damage to DNA o Depurination (purine loss)-mutation in which a pyrine (adenine or Guanine) is removed by a hydroxyl through hydroylysis, 10,000 times per day in typical human cell Results in an apurinic site (no purine) which is later removed o Deamination -results in a C/G to T/A transition via Uracil, cyotisine deaminates into Uracil which deaminates into Thymine o Oxidative Damage to DNA- superoxide radicals hydrogen peroxide, and hydroxyl radicals cause damage to DNA which cause transversions when binding to Adenine. Ex. 8-Oxo-7- hydroeoxyguanosine and Thymidine Glycol Replication Slippage – new strand mispairs with old strand, can lead to expanded trinucleotide repeats o Huntington Disease, Friedreich’s ataxia, myonotic dystrophy, spinocerebellar ataxia type 1 o Fragile X – repeat of CGG sequence, normal 6-54, permutations, 50-200, offspring have 200- 1300, leads to decreased axpression of FRM-1 gene o Huntington’s Disease-repeat of trinucleotide, loss of Huntington gene has no phenotype, mutation is dominant autosomal, expansion of poly-glu tract, leads to disruption of CREB binding protein Mutagens o Base Analogs- similar to normal nitrogen bases but during replication they can cause incorrect nucleotides to be inserted opposite them , Ex. 5-bromouricil o Ultraviolet Light- alters DNA, called photoproducts, that unite adjacent pyrimidine residues in the same strand, forms dimmers, ex. Cyclobutane pyrimidne dimer and 6-4 photo products o Base Altering Agents – alter bases so they will form a mispair, alkylating agents add alkyl groups to positions on the four bases. Ex. Guanine + alkyl group+ oxygen leads to a direct mispairing with thymine results in a GC to AT transition in the next round of replication o Ionizing Radiation- results in ionized and excited molecules that can damage DNA, which leads to oxygen species that lead to different degradation products and mutations can also directly damage DNA by breaking bonds and leading to the formation of apurinic or apyrimidinc sites o Intercalating Agents – proflavin, acridine orange, and chemicals ICR that mimic base pairs and are able to slip themselves between stacked nitrogen bases at the core of the DNA double helix, cause insertion or deletion of a single base pair Cell Response to Damaged DNA- repair or reversal, cell cycle arrest, apoptosis o Repair Strategies
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Photolyse- repairs Thymine-Thymine UV induced dimer Alkyltransferase- enzyme removes alkyl group from alkylation-induced mispairing Base Excision Repair-AP endonuclease- AP endonuclease removes stretch of bad DNA and DNA polymerase fills the gap with complementary nucleotides Mismatch Repair – removes mismatched base pair by determining the correct base pair by keeping the base from the methylated parent strand Nucleotide Excision Repair-
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