Chapter 8.3: Nucleic Acid Chemistry

• The role of DNA as a repository of genetic information depends in part on its inherent stability.
• Chemical transformations are generally very slow in the absence of enzyme catalysts.
• Carcinogenesis and aging may be linked to slowly accumulating, irreversible DNA alterations.
• Denaturation, or melting, of the double helix occurs due to pH extremes or high temperatures because it disrupts hydrogen bonds and base stacking interactions.
• Covalent bonds are not broken when DNA is subjected to extreme pHs.
• The process of separating strands of a DNA double helix is known as denaturation.
• Annealing is the process by which two stands spontaneously rewind when temperature or pH is returned to its normal range.
• Annealing is a two step process.
• The hypochromic effect is the observed decrease in the absorption of UV light when complementary strands are paired.
• The hyperchromic effect is the observed increase in the absorption of UV light when a double stranded nucleic acid is denatured.
• Monitoring UV absorption at 260nm can detect the transition from double stranded to single stranded DNA.
• Denaturation temperature, tm, is the temperature at which half of DNA is present as separated single strands.
• Denaturation temperature increases with the content of guanine cytosine base pairs.
• Denatured regions of partially denatured DNA forms bubbles.
• The denatured bubbles are often rich in adenine thymine base pairs.
• RNA duplexes are more stable to heat denaturation than DNA duplexes.
• RNA DNA hybrid stability is generally intermediate.
• Mutations are alterations in DNA structure that produces permanent changes in the genetic information encoded.
• Deamination is the spontaneous loss of exocyclic amino groups.
• The deamination of cytosine to uracil has around 100 events a day.
• Deaminated cytosine to uracil is recognized as foreign to DNA and is removed. This is almost certainly why DNA contains thymine rather than uracil.
• Deamination of cytosine

  A) Cytosine

  B) Uracil

  
• Deamination of 5-methylcytosine

  A) 5-methylcytosine

  B) Thymine

  
• Deamination of adenine

  A) Adenine

  B) Hypoxanthine

  
• Deamination of guanine

  A) Guanine

  B) Xanthine

  C) Deamination

  
• Depurination is the hydrolysis of the N-beta-glycosyl bond between the base and pentose.
• Depurination creates an apurinic or apyrimdinic, AP, site or abasic site.
• Depurination is more common with purines
• Depurination of guanine

  A) Depurination

  B) Guanosine residue

  C) Guanine

  D) Water

  E) Apurinic residue

  
• UV light causes cyclobutane pyrimidine dimers and 6-4 photoproduct.
• Ionizing radiation, like in x rays and gamma rays, cause ring opening, base fragmentation, and breaks in the covalent backbone of nucleic acids.
• UV radiation

  A) DNA

  B) UV radiation

  C) cyclobutane thymine dimer

  D) 6-4 photoproduct

  
• Nitrous acid precursors are deaminating agents.
• Alkylating agents generate modified nucleotides nonenztmatically
• Some deaminating agents are sodium nitrite, sodium nitrate, and nitrosamine.
• Some alkylating agents are S-adenosylmethionine (SAM), dimethylnitrosamine, dimethylsulfate, and nitrogen mustard.
• S-adenosylmethionine

  
• Alkylating agents can methylate guanine to O6-methyl-guanine, which cannot base pair with cytosine.
• O6-methylguanine

  
• Reactive oxygen species, like hydrogen peroxide, hydroxyl radicals, and superoxide radicals, damage DNA.