Lecture #6 :
DNA and RNA Structure-I
Recommended reading:
Chapter 6 – DNA and RNA structure
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Today’s lecture content:
① The building blocks of DNA
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the four bases of DNA,
the sugar,
the phosphate, and
the epigenetic modifications…
② The double helix of DNA
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the phosphodiester bond,
the hydrogen bonds between bases,
the structure of the double helix,
unusual DNA structures
③ Synthetic Synthesis of DNA
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① The building blocks of DNA
• The deoxyribonucleotides contain three components that
each have properties important for the structure of DNA:
• four different bases possible
• a sugar
• a phosphate
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① The building blocks of DNA
 The four bases of DNA
• DNA contains four bases derivatives of purine or pyrimidine
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① The building blocks of DNA
 The four bases of DNA
• Why did cells choose to have Thymine in DNA and Uracil in
RNA?
 Maybe because 1 of every 107 cytosine is spontaneously
deaminated into uracil (100 events per cell/ per day!)
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① The building blocks of DNA
 The sugar
• The D-deoxyribose exists only in its closed-ring form in DNA
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① The building blocks of DNA
 The sugar
• 4 of the atoms of the ring lay in one plane
• The fifth (either C-2’ or C-3’) is out of the plane
• The most common form of DNA contains a C-2’ endo form,
which has important consequences for the structure of the
double helix
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① The building blocks of DNA
 The Phosphate
• Prior to their incorporation into DNA the nucleotides are
under a nucleotide tri-phosphate form
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① The building blocks of DNA
 The epigenetic modifications
• Some bases in DNA can be modified by the addition of methyl
groups.
• The most conserved one is the
methylation on the carbon 5 of
Cytidines
• In mammalian cells,
methylation of cytosines within
CpG repeats is associated with
repression of gene expression
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Today’s lecture content:
 The building blocks of DNA




the four bases of DNA,
the sugar,
the phosphate, and
the epigenetic modifications…
② The double helix of DNA




the phosphodiester bond,
the hydrogen bonds between bases,
the structure of the double helix,
unusual DNA structures
③ Synthetic Synthesis of DNA
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② The double helix of DNA
• The DNA in the double helix form is called double
stranded DNA, or dsDNA
• dsDNA is formed through the interaction of two
complementary and antiparallel molecules of single
stranded DNA, or ssDNA
3’OH
5’P
+
ssDNA
5’P
3’OH

5’P
Watson Strand
3’OH
Crick Strand
5’P
dsDNA
3’OH
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② The double helix of DNA
• KEY CONVENTION:
When a ssDNA sequence is given, it is written and read in the
direction going from the free 5’-P to the free 3’-OH, left to right
When a double-stranded sequence is shown, the top strand is
written in the 5' → 3’ direction.
The various representations of a nucleotide sequence, using a
pentanucleotide as example, are:
5'-ACGTA-3', or
ACGTA, or
pA-C-G-T-AOH, or
pApCpGpTpA, or
pACGTA,
where p denotes the monophosphate, and a subscript OH
denotes a 3'-hydroxyl group.
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② The double helix of DNA
 The phosphodiester bond
• In one strand of DNA, two
consecutive nucleotides are
connected to each other by a
phosphodiester bond
• The bond is formed between
the 3’OH of the “n” nucleotide
with the 5’P of the next “n+1”
nucleotide
• These bonds are formed by
specialized enzymes during
DNA replication or DNA
synthesis coupled to DNA repair
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② The double helix of DNA
 The hydrogen bonds between the bases
• Two strands of DNA interact to form a double stranded form
through hydrogen bonds between complementary bases:
• Two hydrogen bonds between A and T
• Three hydrogen bonds between G and C
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② The double helix of DNA
 The structure of the double helix
• The two strands of DNA do not lie flat, but form a double helix!
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② The double helix of DNA
 The structure of the double helix
• The DNA helix is usually right
handed
• The two sugar-phosphate
backbones lies on the outside
• The bases are stacked due to
hydrophobic, van der Waals
and electrostatic interactions
• The turn of the helices creates
a major and a minor groove
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② The double helix of DNA
 The structure of the double helix
• Watson and Crick proposed the double helix structure of DNA
in two famous articles in the journal Nature in 1953
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② The double helix of DNA
 The structure of the double helix
• What led Watson and Crick to propose the double helix structure
of DNA?
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② The double helix of DNA
 The structure of the double helix
• What led Watson and Crick to propose the double helix structure
of DNA?
• Edwin Chargaff’s work on the composition of DNA from
different species
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② The double helix of DNA
 The structure of the double helix
• What led Watson and Crick to propose the double helix structure
of DNA?
• Edwin Chargaff’s work on the composition of DNA from
different species:
1) The ratios of A to T, and G to C are identical:
%A=%T
%G=%C
2) The GC content (%G+C) differs among species but is
constant in all cells of an organism within a species.
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② The double helix of DNA
 The structure of the double helix
• What led Watson and Crick to propose the double helix structure
of DNA?
• Rosalind Franklin’s famous
Photograph 51 revealing a
particularly well-resolved xray diffraction pattern of a
DNA fiber
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② The double helix of DNA
 The structure of the double helix
• What led Watson and Crick to propose the double helix structure
of DNA?
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② The double helix of DNA
 The structure of the double helix
"It has not escaped our notice that
the specific pairing we have
postulated immediately suggests
a possible copying mechanism for
the genetic material.”
Watson and Crick, Nature 1953
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② The double helix of DNA
 The structure of the double helix
Rosalind Franklin
1920-1958
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② The double helix of DNA
 Other structures of the double helix
• The structure proposed by
Watson and Crick is the
most common structure
that DNA can form, the B
form.
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② The double helix of DNA
 Other structures of the double helix
• Other structures that are detected in vitro contain short triple
or quadruple helices that contain unusual pairings of bases
• These structures form from sequences with biased
compositions in A:T or G:C
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② The double helix of DNA
 Other structures of the double helix
• Other structures are detected in vitro in the case of inverted
repeats, which can form a cruciform (double-hairpin) structure
• The corresponding sequences in vivo are correlated with genome
instability
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Today’s lecture content:
 The building blocks of DNA




the four bases of DNA,
the sugar,
the phosphate, and
the epigenetic modifications
 The double helix of DNA




the phosphodiester bond,
the hydrogen bonds between bases,
the structure of the double helix,
unusual DNA structures
③ Synthetic Synthesis of DNA
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③ Synthetic synthesis of DNA
• Oligonucleotides are short chains of single-stranded DNA (< 50
bases)
• Oligonucleotides can easily be chemically synthesized
• The synthesis occurs in the 3' → 5’ direction!
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③ Synthetic synthesis of DNA
• Recent advances in gene synthesis have made it possible to
synthesize larger DNA fragments
• DNA nanotechnology, aims to make intelligent nanostructures
through the assembly of DNA!
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Next Lecture:
#7 – DNA and RNA Structure - II
On Wednesday, February 6th
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