Thursday, 21 February 2013

DNA is a double helix


The observation that the bases are present in different amounts in
the DNAs of different species led to the concept that the sequence
of bases is the form in which genetic information is carried. By the
1950s, the concept of genetic information was common: the twin problems
it posed were working out the structure of the nucleic acid, and explaining
how a sequence of bases in DNA could represent the sequence
of amino acids in a protein.
Three notions converged in the construction of the double helix
model for DNA by Watson and Crick in 1953:
• X-ray diffraction data showed that DNA has the form of a regular
helix, making a complete turn every 34 A (3.4 nm), with a diameter
of ~20 A (2 nm). Since the distance between adjacent nucleotides is
3.4 A, there must be 10 nucleotides per turn.
• The density of DNA suggests that the helix must contain two
polynucleotide chains. The constant diameter of the helix can be
explained if the bases in each chain face inward and are restricted
so that a purine is always opposite a pyrimidine, avoiding partnerships
of purine-purine (too wide) or pyrimidine-pyrimidine (too
narrow).
• Irrespective of the absolute amounts of each base, the proportion
of G is always the same as the proportion of C in DNA,
and the proportion of A is always the same as that of T. So the
composition of any DNA can be described by the proportion
of its bases that is G + C. This ranges from 26% to 74% for
different species.
Watson and Crick proposed that the two polynucleotide
chains in the double helix associate by hydrogen bonding between
the nitrogenous bases. G can hydrogen bond specifically
only with C, while A can bond specifically only with T. These
reactions are described as base pairing, and the paired bases (G
with C, or A with T) are said to be complementary.
The model proposed that the two polynucleotide chains
run in opposite directions (antiparallel), as illustrated in Figure
1.8. Looking along the helix, one strand runs in the 5'—>3' direction,
while its partner runs 3'—»5'.
The sugar-phosphate backbone is on the outside and carries
negative charges on the phosphate groups. When DNA is in solution
in vitro, the charges are neutralized by the binding of
metal ions, typically by Na+. In the cell, positively charged proteins
provide some of the neutralizing force. These proteins play an important
role in determining the organization of DNA in the cell.
The bases lie on the inside. They are flat structures, lying in pairs
perpendicular to the axis of the helix. Consider the double helix in terms of a spiral staircase: the base pairs form the treads, as illustrated
schematically in Figure 1.9. Proceeding along the helix, bases are
stacked above one another, in a sense like a pile of plates.
Each base pair is rotated ~36° around the axis of the helix relative to
the next base pair. So ~10 base pairs make a complete turn of 360°. The
twisting of the two strands around one another forms a double helix
with a minor groove (~12 A across) and a major groove (~22 A across),
as can be seen from the scale model of Figure 1.10. The double helix is
right-handed; the turns run clockwise looking along the helical axis.
These features represent the accepted model for what is known as the
B-formofDNA.
It is important to realize that the B-form represents an average, not a
precisely specified structure. DNA structure can change locally. If it
has more base pairs per turn it is said to be overwound; if it has fewer
base pairs per turn it is underwound. Local winding can be affected by
the overall conformation of the DNA double helix in space or by the
binding of proteins to specific sites.

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