The document discusses the tertiary structure of DNA. It explains that DNA folds into specific 3D shapes, including B-DNA, A-DNA, and Z-DNA. B-DNA is the most common form found in vivo, forming a narrow, elongated double helix. A-DNA is shorter and wider, while Z-DNA has a left-handed helix. The document also describes how DNA is packaged in the cell nucleus through association with histone proteins to form nucleosomes, which coil the DNA into higher-order chromatin structures in the chromosome.

1. DNA Higher organization
(Tertiary) Structure
By
R Wanyama

2. Polynucleotides (1)
• Polynucleotides are formed by the
condensation of two or more nucleotides.
The condensation most commonly occurs
between the alcohol of a 5'-phosphate of
one nucleotide and the 3'-hydroxyl of a
second, with the elimination of H2O,
forming a phosphodiester bond. The
formation of phosphodiester bonds in DNA
and RNA exhibits directionality.

3. Polynucleotides (1)
• The primary structure of DNA and RNA
(the linear arrangement of the nucleotides)
proceeds in the 5'—>3' direction. The
common representation of the primary
structure of DNA or RNA molecules is to
write the nucleotide sequences from left to
right synonymous with the 5'—>3' direction
as shown:
• 5'–pGpApTpC–3'

4. DNA: structure
• Like RNAs, deoxyribonucleic acids (DNAs)
are polymeric molecules consisting of
nucleotide building blocks.
• Instead of ribose, however, DNA contains 2-
deoxyribose, and the uracil base in RNA is
replaced by thymine.

6. Tertiary Structures of DNA
• Tertiary structure is the locations of the atoms
in three-dimensional space, taking into
consideration geometrical and steric constraints
• A higher order than the secondary structure in
which large-scale folding in a linear polymer
occurs and the entire chain is folded into a
specific 3-dimensional shape

7. Tertiary Structures of DNA
• There are 4 areas in which the structural
forms of DNA can differ
• Handedness - right or left
• Length of the helix turn
• Number of base pairs per turn
• Difference in size between the major and
minor grooves

8. Tertiary Structures of DNA
• The tertiary arrangement of DNA's double
helix in space includes
– B-DNA,
– A-DNA
– Z-DNA
• B-DNA is the most common form of DNA in
vivo and is more narrow, elongated helix than
A-DNA

9. B-DNAs
• Its wide major groove makes it more accessible
to proteins
• It has a narrow minor groove
• B-DNAs favored conformations occurs at high
water concentrations and the hydration of the
minor groove appears to favor B-DNA
• B-DNA base pairs nearly perpendicular to
helix axis

10. • The sugar pucker which determines the
shape of the α-helix, whether the helix will
exist in the A-form or in the B-form occurs
at the C2'-end

11. A-DNA
• Is shorter and wider than helix B
• Most RNA and RNA-DNA duplex in this
form
• A-DNA has a deep, narrow major groove
which does not make it easily accessible to
proteins
• On the other hand, its wide, shallow minor
groove makes it accessible to proteins but
with lower information content than the
major groove

12. A-DNA
• Its favored conformation is at low water
concentrations.
• A-DNAs base pairs tilt to helix axis and are
displaced from axis

13. Z-DNA
• Is a relatively rare left-handed double-helix
• Given the proper sequence and superhelical
tension, it can be formed in vivo but its
function is unclear
• It has a more narrow, more elongated helix
than A or B.
• Z-DNA's major groove is not really groove and
it has a narrow minor groove
• The most favored conformation occurs when
there are high salt concentrations

14. Forms of DNA

15. Each of us has enough DNA to
reach from here to the sun and
back, more than 300 times. How
is all of that DNA packaged so
tightly into chromosomes and
squeezed into a tiny nucleus?

16. The Problem
• Spacing between base pairs ≈3.4Å
• For human genome, approximately 3.2 billion
base pairs
• Total length≈ 3.4×10-10×3.2×109×2 ≈2.2m
• Diameter of a nucleus: 5~10×10-6m
• Access to genetic information must be
regulated
• DNA are packaged with associated proteins
into chromosomes

17. DNA, Histones, and Chromatin (1)
• The answer to this question lies in the fact
that certain proteins compact chromosomal
DNA into the eukaryotic nucleus
• These proteins are called histones, and the
resulting DNA-protein complex is
called chromatin
• Histones are a family of small, positively
charged proteins termed H1, H2A, H2B, H3,
and H4

18. DNA, Histones, and Chromatin (2)
• DNA is negatively charged, due to the
phosphate groups in its phosphate-
sugar backbone, so histones bind with DNA
very tightly
• Packaged DNA must provide controlled
access to regions required for gene
expression

19. HISTONES
• Main packaging proteins
• 5 classes: H1, H2A, H2B, H3, H4.
• Rich in Lysine and Arginine

20. The Nucleosome: The Unit of
Chromatin
• The basic repeating structural (and
functional) unit of chromatin is the
nucleosome, which contains nine histone
proteins and about 166 base pairs of DNA
• Two, each of the histones H2A, H2B, H3,
and H4 come together to form a histone
octamer, which binds and wraps about 1.7
turns of DNA, or about 146 base pairs

21. • The addition of one H1 protein wraps
another 20 base pairs, resulting in two full
turns around the octamer
• Obviously, 166 base pairs are not very much,
as each chromosome contains over 100
million base pairs of DNA on average

22. • Therefore, every chromosome contains
hundreds of thousands of nucleosomes, and
these nucleosomes are joined by the DNA
that runs between them
• This joining DNA is referred to as linker
DNA
• Each chromosome is thus a long chain of
nucleosomes, which gives the appearance of
a string of beads when viewed using an
electron microscope

23. Chromatin is Coiled into Higher-
Order Structures (1)
• The packaging of DNA into nucleosomes
shortens the fiber length about sevenfold. In
other words, a piece of DNA that is 1 meter
long will become a "string-of-beads"
chromatin fiber just 14 centimeters (about 6
inches) long
• Despite this shortening, a half-foot of
chromatin is still much too long to fit into
the nucleus, which is typically only 10-20
microns in diameter

24. Chromatin is Coiled into Higher-
Order Structures (2)
• Therefore, chromatin is further coiled into an
even shorter, thicker fiber, termed the "30-nm
fiber," because it is ~30 nanometers in
diameter
• The precise structure of the 30-nm fiber is
not yet known
• ~40 folds in packaging
• Chromatin structure beyond nucleosomes is
poorly understood