DNA Biochemistry

Biochemistry of heredity:
the structure of Deoxyribonucleic Acid (DNA)

In principle: Genes are made of nucleic acids

The Watson-Crick structure for Deoxyribonucleic acid (DNA) (1953)
          a double-stranded helix
          sugar-phosphate backbone outside
          nitrogenous bases (A,C,G, T) inside
          bases held together by hydrogen bonds ( H- or hydrostatic bonds )
          Fundamental insight:
             base pairing follows specific rules:
                 A+T , G+C
             each pair has similar structure

Building blocks of nucleic acids (DNA & RNA)
bases
     pyrimidines (single ring)
       cytosine(C)       thymine (T)        [ uracil in RNA (U) ]
          "PYRamids were CUT from stone"

    purines (double ring)
       adenine (A)     guanine (G)
          "AGs are PURe"

nucleoside = base + sugar
deoxyribose sugar in DNA (- H on 2'-C)

nucleotide = nucleoside + phosphate(s) [PO₄]
deoxyadenosine monophosphate (dAMP)
deoxyadenosine-5'-phosphate or deoxyadenylic acid

   polynucleotide = nucleotide + nucleotide + nucleotide + etc
       nucleotides are linked by 3' 5' phosphodiester bonds
     ***polynucleotides have directionality***
                phosphoryl (5') & hydroxyl (3') ends

Structure of B-DNA   (3-D model from CSHL)
     1) Two plectonemic (twisted) right-handed polynucleotide strands: a double helix
     2) Strands antiparallel wrt 5' 3' orientation
     3) Strands held together by hydrogen (H-) bonds
     4) H-bonds follow specific base-pairing rules
            A pairs with T: two H-bonds
            G pairs with C: three H-bonds
            A+T & G+C pairs have very similar shapes & sizes
     5) Base pairs co-planar: interval = 0.34 nM
     6) Period of helix 10 bp (base pairs) = 3.4 nM
     7) 3-D structure has major & minor grooves
     8) Order of bases in each strand aperiodic

Homework #2
Homework #3

Other structures for nucleic acids
     A-DNA: not groovy, base pairs not co-planar
     Z-DNA: left-handed helix
     Ribonucleic Acid (RNA):
             substitute uracil for thymine [ thymine = 5-methyl-uracil ]
                             ribose sugar for deoxyribose
             typically single-stranded / complex double-stranded folding:
               mRNA (messenger RNA): long, single-stranded
                rRNA (ribosomal RNA): medium-sized, complex 'stem & loop' folding
                tRNA (transfer RNA): small, 'cloverleaf' structure
              RNA viruses (e.g., Covid-19)

Implications of DNA structure for its genetic function

"The sequence of bases on a single chain does not appear to be restricted in any way....
It has not escaped our notice that the specific pairing we have postulated
immediately suggests a possible copying mechanism for the genetic material."
(Watson & Crick 1953. Nature 112:753)

DNA an aperiodic crystal:
order of bases conveys information

Antiparallel strands are self-complementary:
DNA potentially autocatalytic