MCB 31. Sp 2008
Lecture 3, January 30
DNA: The Double Helix
I. The conundrum
A. DNA seemed to simple to encode
information carried by genes. DNA is a polymer of nucleotides, of which
there are only 4 kinds, A,G,T, and C. Yet, bacterial
transformation, and other kinds of experiments, clearly pointed to DNA.
B. The most complex type of molecule in
cells is protein, composed of 20 different kinds of amino acids ( monomer)
strung together into a protein or poly peptide ( polymer).
C. Polymers are molecules in which
similar repeating units ( monomers) are strung together, held by chemical
bonds, like beads on a string. Plastics (teflon) and fibers ( nylon) are
polymers. So are proteins and nucleic acids ( DNA and RNA). There are also
polymers of sugar monomers, polysaccharides.
II. Would an
understanding of the 3D structure of DNA provide a clue on how it could encode
and transmit genetic information? The answer, published in 1953, astonished the
scientific community, and is the bedrock of the "new biology".
A. The Players
1. Jim Watson,
a new Ph.D. from Indiana University, who went to Cambridge, England ( via
Copenhagen) on a post-doctoral fellowship. Interested in inheritance ,
especially in viruses.
2. Francis Crick.
Still grinding away at getting a Ph.D. in Cambridge, working on the structure
of proteins using X-ray crystallography.
3. Maurice Wilkins, a
Professor and physical chemist in London interested in protein and DNA
structure.
4. Rosalind Franklin,
a research associate of Wilkins who perfected methods for looking at DNA with
x-rays.
5. Linus Pauling. The
world's most celebrated chemist, at Cal Tech, who had made a break through in
analysis of protein structure using x-ray crystallography and model building.
6. Ewin Chargaff, a
biochemist working at Columbia who analyzed the composition of monomers ( A,T,G
& C) in different DNAs.
B. The Search.
1. A belief that the structure of DNA was the key to
understanding how it worked.
2. A belief that model building of DNA was the route to
understanding.
3. Tools: Crick's theory of
diffraction of helices. Franklin's X-ray analysis,
model building. How to
place the strings and dangles of the polymer. What goes outside and what goes
inside and how many strands are there?
III. The Structure
A. Hydrogen bonding of
nucleotide monomers to one another. Chargaff's rule: A=T, G=C.
B. A double stranded helix
of DNA polynucleotides with nucleotides on the inside, held together by AT and
GC hydrogen bonds.
C. The structure is
redundant. Once you know the sequence in one strand you have specified the
order in the other. The strands are complementary.
1.
This structure shows how DNA could
be faithfully passed on from parent to daughter cell. Each daughter cell
gets one strand of DNA and the complementary strand is assembled on the
template of the parent strand.
IV. Some questions:
A. How could this
hypothesis of complementary strands giving rise to a conservative inheritance
of DNA be proved? Or disproved?
B. Could single
stranded DNA ( or RNA) also act as a gene? Retroviruses.
(See pp. 582-84 in the text if you want to know more on this.)
C. Could any
substance other than DNA or RNA act as a gene? Prions.
( See pp. 628-29 for more on prions if you want to more on this.)
V. Concepts to Know
1. DNA is a double
stranded helix composed of hydrogen bonded complementary base pairs.
2. Terms to know:
nucleotide, monomer, polymer, helix, ATGC