DNA organization

1. DNA Organization
Dr. Eman Badr
Medical Biochemistry
and Molecular Biology

2. ILOs
1. Define chromatin, nucleosomes and histone
proteins
2. Illustrate levels of DNA organization

3. DNA organization
• Definition: - DNA organization is the process by which
the very long DNA molecules are packaged inside the
nucleus.
• Chromatin: -
– Def: - It is the chromosomal material extracted from nuclei
of cells of eukaryotic organisms.
– It consists of:-
1. Very long double stranded DNA molecules.
2. Histones: - these are small basic proteins.
3. Non-histone proteins: - like enzymes involved in DNA
replication such as topoisomerases and transcription
such as RNA polymerase.
4. Small quantity of RNA.

4. • Histones:-
– Def: - These are closely related basic proteins (they are positively
charged proteins rich in basic amino acids as arginine and lysine)
– There are 4 types:- H1, H2 (H2A, H2B) , H3 and H4.
– H1 histones are the one least tightly bound to chromatin
– The organizational unit of chromatin is called nucleosome
• Nucleosomes:-
– Def: - These are dense spherical structures containing DNA and
histones.

5. • The DNA is supercoiled in a left-handed helix
over the surface of the disc-shaped histone
octamer.
• Each nucleosome is separated by 30 bp linker
region of DNA.
• Nucleosomes appear like beads on a string.
• H1 histone helps in super-packing of
nucleosomes in the nuclei.

6. Higher ordered structures of
compact chromatin
1. The 10-nm fibril:-
– The disc like nucleosome structure has a 10-nm
diameter and a height of 5 nm.
– It produces a 10 folds shortening of the DNA.
– The nucleosomes are arranged with their flat surfaces
parallel with the fibril axis.
2. The 30-nm fiber:-
– The 10-nm fibril is supercoiled with 6 or 7
nucleosomes per turn to form 30-nm chromatin fiber.
– It produces 40-60 folds shortening of the DNA.
– H1 histones stabilize the 30-nm fiber.

7. 3. Formation of loops:-
– The 30-nm fibers are folded into a series of looped
domains anchored in a supporting matrix within
the nucleus forming the 300-nm non-condensed
loops; with more condensation, the 700 nm then
1400 nm chromosome is formed.
– It produces 8000 folds shortening of the DNA.
4. Chromosome:-
– It consists of 2 sister chromatids connected at a
centromere.
– The centromere is A-T rich region.

8. • The ends of each chromosome are called
telomeres.
• Telomeres are T-G rich sequences synthesized
by an enzyme called telomerase that controls
the length of telomeres.
• Telomere shorting has been associated with
both malignant transformation and aging.
• Now; Telomerase has become target for
cancer chemotherapy and drug development.

10. According to density of chromatin, 2
types are known
1. Euchromatin: - Less dense and
transcriptionally active.
2. Heterochromatin: - More dense and
transcriptionally inactive there are two types of
heterochromatin.
– Constitutive heterochromatin:- It is always condensed
and thus inactive, I is found in regions near the
centromere and at the telomeres.
– Facultative heterochromatin:- sometimes it is
condensed and in other times it is less condensed and
appear as euchromatin e.g. one of the X-
chromosomes of females is active only during
gametogenesis , then become inactive.

11. Mitochondrial DNA (mt DNA)
• Human mitochondria contain 2 to 10 copies of
a small circular doubl-stranded DNA molecule.
• Mt DNA forms about 1% of the total cellular
DNA.
• Mt DNA codes for (2 mt rRNA, 22 mt tRNA and
13 proteins) that play a role in respiratory
chain.

12. Features of mt DNA:-
1. It is circular, double-stranded
2. Encodes 13 protein subunits of the
respiratory chain (of total of about 67).
3. Encodes large (16s) and small (12s) mt
ribosomal RNAs.
4. Encodes 22 mt tRNA molecules.
5. High mutation rate (5 to 10 times of nuclear
DNA).
6. Completely maternally inherited.