DNA Organization

I.

DNA Importance
DNA of a
chromosome
Process : crossing over,
recombination, tranposition,
and conversion.

Genetic
information

MUTATION FACTORS : viruses,

chemicals, UV, ionizing
radiation

II.

DISEA

Chromatin is the chromosal material in nucleic cell of

eukaryotic

Chromatin

DNA Molecules

Very long doublestranded DNA helix

has a length that
thousands times the
diameter of cell

histones

nonhiston

Small quantity
of RNA

Enzyms
Proteins that
involved in
involved in RNA
DNA
Synthesis,
processing and
III.
Histones are the most abundant chromatin proteins
transport into
cytoplasm
Organizational unit of soluble
chromatin is the nucleosome. Soluble

chromatin have 4 types of histones. They are H2A, H2B, H3, and H4. Actually,
histones are a small family of closely related basic proteins. The structure of
this histones have been highly conserved between species. They are identical
in all eukaryotes This 4 histones are subject to 6 types of covalent
modification, acetylation, methylation, phosphorylation, ADP-ribosylation,
monoubiquitylation, and sumoylation.
IV.

Nucleosomes contain histone and DNA

When the histone octamer is mixed with purified, Double-stranded DNA

under appropriate ionic conditions, the same x-ray diffraction patterns is
formed as that observed in freshly isolated chromatin. Futhermore, the
reconstitution of nucleosome from DNA and the histones are independent of
the organismal of cellular origin of the various components.

The amino terminal tails of all histones probably extend outside of the
structure and are available for regulatory covalent modifications
For ex : ADP-ribosylation of histones is associated with DNA repair (see
table 35-1 page 313(harper) )

The (H3-H4)2 tetramer itself can confer nucleosome-like properties on

DNA, so has a central role in the formation. Histones dimers (H2A-H2B)
stabilizes the primary particle and firmly binds two additional half-turns of
DNA previously bound only loosely to the (H3-H4) 2. Thus 1,75 superhelical
turns of DNA are wrapped around the surface of histone octamer, protecting
146 base pairs of DNA and forming the nucleosome particle. Core particle are
separated by 30-base pairs regionn termed linker. Repeating og this
structures called beads on string. The assembly of nucleosomes is
facilitated by histone chaperones, a group of proteins that exhibit high-affinity
histone binding as the histone is assembled, histones are released from the
histone chaperons.
V.

High-Ordered Structures of chromatin

2 higher orders of structure, 10-nm fibril and 30-nm chromatin fiber.
The 10-nm fibril consist of nucleosomes arranged with edges separated by a
smalll distance

6 or 7 nucleosomes of 10-nm fibril form the 30-nm chromatin fiber.

H1 histones appear to stabilize the 30-nm fiber, but their position and that
of variable length spacer DNA are not clear, so nucleosomes can form a
variety of packed structures.
mitotic chromosome
fold.

: 30-nm fiber must be compacted in legth 100-

Interphase chromosomes : chromatin fibers appear to be organized into

30.000-100.000 bp

DNA sequences may be located nonrandomly. It has been suggested that

each looped domain of chromatin corresponds to one or more genetic
functione, containing both coding and noncoding regions.
VI .

ACTIVE AND INACTIVE REGIONS OF CHROMATIN

Every cell contains some genetic information, but the difference between
cells is caused by differential gene expression
Chromatin contain active gene (potentially transcriptionally). DNA in active
chromatin contains large regions (about 100.000 bases long) and more
sensitive to digest by a nuclease such as DNAse I . DNAse I makes singlestrand cuts in any segment of DNA.
Chromatin also contains inactive
gene (transcriptionally inactive
chromatin) is densely in packed
during interphase referred to as
heterochromatin,
but
for
transcriptionally active stains
less
densely
referred
to
euchromatin.
Chromatin
in
inactive region often high in
meC content and the histones
relatively
lower
levels
of
covalent modifications.

Constitutive heterochromatin : always

condensed, inactive. Found in

Facultative heterochromatin :
At times condensed, but other times
actively transcribed, and thus
uncondensed and appears as
euchromatin

in

and
heterochromati
n

VII .

DNA IS ORGANIZED INTO CHROMOSOMES

At metaphase, mammalian create identical duplicated called sister

chromatids and connected at a centromere. This centromoere is bound by

histone H3 variant protein CENP-A, and other proteins, this complex bound is
called kinetochore. Kinetochore act as anchor for mitotic spindle so this is
essential for segregation during mitosis.
The end of each chormosome is called telomeres. It consists of TG-rich
repeats. Telomere is a multisubunit RNA-containing complex related to viral
RNA-dependetn DNA Polymerase. This enzyme s responsible for telomere
synthesis and thus for maintaining the length of telomere.
Telomerase become an attractive target for cancer chemotherapy and drug
development because it has been associated with both malignant
transformation and aging.

VIII.

Coding regions

The protein coding regions of DNA as a single mRNA molecules, are usuallly
interrupted by large intervening sequences of nonprotein coding DNA. The
primary transcripts of DNA, mRNA precursors, contain noncoding intervening
sequences of RNA that must be removed to form mature mRNA. Introns
removed to form mature RNA (only extrons). Introns may serve to separate
exons (functional) of coding information to permit genetic rearrangement by
recombination to occur more rapidly.
VIII.

Redundant and not highly transcribed genome

Haploid genome consists of 3 x 109 bp of DNA subdivided into 23

chromosomes. However, studies of mutation rates suggest that humans have
fewer than 100,000 proteins encoded by the 1% of thehuman genome that
is composed of exonic DNA. There are <25,000 non-protein-coding, this
means they are never translated into amino acid sequence of a protein
molecule. Depending on the lenght, repetitive sequence is divided into two
types, they are LINEs (Long Interspread repeat sequnces and SINEs (Short
interspread repeat sequences).
Repeat sequences consist 2-6 bp repeat up to 50 times. The microsatellite
sequences are commonly found repeats of AC in one strand and TG in
opposite strand but sometimes including CG, AT, and CA.
The ease of detecting them using the polymerase chain reaction (PCR). By
using PCR, people can be rapidly screened for a certain microsatellite
polymorphism

The majority of the peptides in mithocondria are coded by nuclear gene found
in mtDNA. A nnumber of diseases have now been shown due to mutations of
mtDNA, this include myopathies, neurologic disorder, diabetes melitus.
IX. GENETC MATERIAL CAN BE ALTERRED ND REARRANGED

Removal and insertion change in the sequence of purine and pyrimidine result
in an altered gene product. Chromosomal recombination is in one way to
rearrange genetic material. Genetic material can be exchanged between
homologous chromosomes. Crossing over is and equal and reciprocal
exchange of genetic information between homologoud chromosomes. Some
bacteriophages ara capable of recombining with DNA. The backbone of the
circular bacteriophage is broken, as is that of the DNA molecule.
Bacteriophage is straightened out (linearized) as it is integrated into DNA
molecule. If bateriophage contains a DNA sequence homologous with DNA
molecule, a recombination between homologous chromosomes can occur.
However, some bacteriophages synthesize proteins that bind specific sites to
a nonhomologous, integration occurs but it is called site specific
When at the S phase, contain a tetraploid content of DNA. Each of the sister
chromatids contains genetical information since each is a product os
semiconservatice replication.
Crossing over can occur between these identical sister chromatids. Of
course,this exchange have no genetic consequence as long as it in an equal
crossover.