DNA is made up of nucleotides containing a sugar, phosphate, and one of four nitrogenous bases. Nucleotides are linked by phosphodiester bonds between the sugar of one nucleotide and the phosphate of the next, forming the DNA backbone. James Watson and Francis Crick developed a double helix model of DNA structure based on x-ray crystallography data showing two anti-parallel strands coiled around a common axis with the bases hydrogen bonding in a specific pattern between strands. DNA is highly condensed in chromosomes through coiling around histone proteins to fit inside the cell nucleus.

1. Section1
Structure of DNA

2. Nucleotides—the monomer units or building blocks of nucleic acids, additionally
They form a part of many coenzymes
serve as donors of phosphoryl groups (eg, ATP or GTP), of sugars (eg, UDP- )
Regulatory nucleotides include the second messengers cAMP and cGMP,
The control by ADP of oxidative phosphorylation,
Allosteric regulation of enzyme activity by ATP, AMP, and CTP.
Synthetic purine and pyrimidine analogs that contain halogens, thiols, or additional
nitrogen are employed for chemotherapy of cancer and as suppressors of the immune
response during organ transplantation.
1.Nucleic acids: DNA and RNA structure

3. Nucleotides have three components
1. a nitrogenous (nitrogen-containing) base,
In RNA, thymine is replaced by uracil

4. a pentose,
a phosphate .
 The molecule without the phosphate group is called a nucleoside.

6. Phosphodiester Bonds Link Successive Nucleotides in Nucleic
Acids
The successive nucleotides are linked through
phosphate-group “bridges,” in which the 5’-P group
of one nucleotide unit is joined to the 3’-OH group
of the next, creating a phosphodiester linkage.
the covalent backbones of nucleic acids
consist of alternating phosphate and pentose
residues, which is hydrophilic and the
nitrogenous bases may be regarded as side
groups.
The base sequence is written in the 5’ -to-3’
direction.

7. The phosphate groups, with a pKa near 0, are completely ionized and negatively
charged at pH 7,
This negative charge repels nucleophilic species such as hydroxide ion;
consequently, phosphodiester linkages are less susceptible to hydrolytic attack.
The absence of the 2 -hydroxyl group in DNA further increases its resistance to
hydrolysis.
The greater stability of DNA probably accounts for its use rather than RNA as the
hereditary material in all modern cells and in many viruses
The human genome comprises approximately 3 billion nucleotides, divided
among 24 distinct DNA molecules (22 autosomes, X and Y sex chromosomes) of
different sizes.

8.  Maurice Wilkins and Rosalind Franklin obtained x-ray diffraction photographs of
fibers of DNA .
 From these and the observation of Chargaff that in DNA molecules the
concentration of deoxyadenosine (A) nucleotides equals that of thymidine (T)
nucleotides (A = T), while the concentration of deoxyguanosine (G) nucleotides
equals that of deoxycytidine (C) nucleotides (G = C), James Watson and Francis
Crick inferred a structural model for DNA.a`
Structural model for DNA

10. Features of the Watson-Crick model
1. Two helical polynucleotide chains are coiled around a common axis.
2. The chains run in opposite directions.
3. The sugar-phosphate backbones are on the outside and, therefore, the purine
and pyrimidine bases lie on the inside of the helix.
4. The bases are nearly perpendicular to the helix axis, and adjacent bases are
separated by 3.4 Å.
5. there are 10 bases (= 34 Å per repeat/3.4 Å per base) per turn of helix.
6. There is a rotation of 36 degrees per base (360 degrees per full turn/10 bases
per turn).
7. The diameter of the helix is 20 Å.

11. The stacking of bases one on top of another contributes to the stability of the
double helix in two ways .
First, adjacent base pairs attract one another through van der Waals forces.
In addition, the double helix is stabilized by hydrophobic interactions between the
bases.
Three hydrogen bonds can form between G and C, symbolized GΞC, but only two
can form between A and T, symbolized A=T.
The sequence of bases of one strand determines the sequence of the other strand;
a G base on one strand is always paired with a C base on the other strand.

12. DNA Molecules Are Highly
Condensed in Chromosomes
The whole DNA/RNA/Protein (histone basic proteins and non-histone transcription
factors and enzymes) content of the nucleus is called the chromatin and
 the complete set of the DNA part is called the genome that is 3.3 x 109 bp in length
for human.
 whole length of a haploid human nuclear DNA is about 1 meter (or 3 feet) while the
whole cell is 20 m and nucleus is 5 -15 m in diameter.
 If the entire DNA in all of the cells in a human body was placed end to end it would
reach the sun and back 600 times (2m, 2X1014cells= 2X1011km, (1.5 X108km).

13. •The DNA has to be condensed to occupy such small space.
This condensation needs to be in a well-organized manner so as to be easily
accessed for transcription, repair and replication.
•This organization requires interaction with several proteins and RNAs.

15.  During interphase chromatin is in its least condensed state and appears loosely
distributed throughout the nucleus.
 Chromatin condensation begins during prophase and chromosomes become visible
under light microscope.
 Chromosomes remain condensed throughout the various stages of mitosis .
 When interphase nuclei are broken open very gently and their contents examined
under the electron microscope, most of the chromatin is in the form of a fiber .

16.  If this chromatin is subjected to treatments that cause it to unfold partially, it can
be seen under the electron microscope as a series of “beads on a string” .
The string is DNA, and
each bead is a
“nucleosome core particle”
that consists of DNA wound
around a protein core formed
from histones.
There are five types of
histones; H1, H2A, H2B, H3
and H4.

17.  Each nucleosome consists of 1.75 superhelical turns (146 nucleotides length) of
DNA wrapped around the core histone barrels-shaped octamers (2 molecules of
each( H2A, H2B, H3 &H4).
 The N-terminus of each octamers subunit is protruding free to be accessible for
covalent modifications.
 A linker stretch of DNA (30 nucleotide in length) connects between the
nucleosome cores and is covered by one molecule of histone H1 so as to close
two turns of DNA
 The histone octamer forms a protein core around which the double-stranded
DNA is wound.

19.  Chromatin packing offers a mechanism for controlling gene expression.
 Highly compacted chromatin simply isn't accessible to the enzymes involved in
DNA transcription, replication , or repair. Regions of chromatin where active
transcription is taking place (called euchromatin) are less condensed
than regions where transcription is inactive or is being actively inhibited or
repressed (called heterochromatin) .

20. There are two types of heterochromatin: constitutive and facultative.
Constitutive heterochromatin is always condensed and thus inactive.
 It is found in the regions near the chromosomal centromere and at chromosomal
ends (telomeres).
Facultative heterochromatin is at times condensed, but at other times it is
actively transcribed and, thus, uncondensed and appears as euchromatin.
 Of the two members of the X chromosome pair in mammalian females, one X
chromosome is almost completely inactive transcriptionally and is
heterochromatic.
 However, the heterochromatic X chromosome decondenses during
gametogenesis and becomes transcriptionally active during early embryogenesis
thus, it is facultative heterochromatin.

21. Possible roles of modified histones.
1. Acetylation of histones H3 and H4 is associated with the activation or
inactivation of gene transcription
2. Acetylation of core histones is associated with chromosomal assembly during
DNA replication.
3. Phosphorylation of histone H1 is associated with the condensation of
chromosomes during the replication cycle.
4. ADP ribosylation of histones is associated with DNA repair.
5. Methylation of histones is correlated with activation and repression of gene
transcription.