DNA Biochemistry

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

In principle: Genes are made of nucleic acids
    The identity of the hereditary substance was unknown until 1940;
        its structure was unknown until 1953
    "Genetics" was taught for 50 years without this information (see Orientation)
     The history of the discovery of DNA is a fascinating detective story

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:
             bases on alternative strands pair according to specific rules:
                 A with T   G with C
             each pair has similar structure

A second form of nucleic acid is ribonucleic acid (RNA)

Homework #1

Building blocks of nucleic acids (DNA & RNA)
bases [IG1_02-04]
     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) [IG1_02-03]

deoxyadenosine (dA) deoxyguanosine (dG)
deoxycytosine (dC) deoxythymidine (dT)

nucleotide = nucleoside + phosphate(s) [PO₄] [IG1_02-02]
one phosphate deoxyucleoside monophosphate (dNMP)
three phosphates deoxynucleoside triphosphate (dNTP)

     deoxyadenosine-5'-phosphate or deoxyadenylic acid
       deoxyadenylic acid (dAMP)    /   deoxyguanylic acid      (dGMP)
         deoxycytidylic acid (dCMP)   /   deoxythymidylic acid   (dTMP)

   polynucleotide = nucleotide + nucleotide + nucleotide + etc [IG1_02-05]
       nucleotides are linked by 3' 5' phosphodiester bonds
     ***polynucleotides have directionality***
              hydroxyl (3') & phosphoryl (5') ends

Structure of B-DNA   (3-D model from CSHL) [IG1_02-06]
     1) Two plectonemic (twisted) right-handed polynucleotide helices (demo)
     2) Helices antiparallel strands wrt 5' 3' orientation
     3) Strands held together by hydrogen (H-) bonds between bases
     4) H-bonds form according to specific base-pairing rules [IG1_02-07]
            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 [= 3.4 Ǻngstroms]
     6) Period of helix is 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 [IG1_02-09, -11] [IG1_02-Tab01]
     A-DNA : not groovy, base pairs not co-planar
     Z-DNA: left-handed helix (demo) [IG1_02-12]
     Ribonucleic Acid (RNA):
             substitute uracil for thymine [ thymine = 5-methyl-uracil ]
                              ribose sugar for deoxy-ribose
             typically single-stranded or with 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
              [more on RNA structures later]

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 is an aperiodic crystal:
order of bases conveys information

Antiparallel strands are self-complementary:
DNA is potentially autocatalytic