Download Organization of Eukaryotic DNA Dr: Hussein abdelaziz

Organization of Eukaryotic DNA
Dr: Hussein abdelaziz
Objectives
By the end of lecture the student should:
 Identify DNA organization
 Define gene and genome.
 Recognize types of genes
 Describe Human Genome Project
Chromatin
 chromosomal material extracted from nuclei of
eukaryotic cells
 Consists of:
1- Very long double stranded DNA molecule (1.7
m long)
2- Proteins involved in folding/packing eukaryotic
chromosomes and consists of:
A- Histone proteins: basic proteins
B- Non-histone proteins: regulatory proteins
including enzymes & regulatory factors of
transcription.
3- Small amount of RNA
Histones
 Five classes of histones,
H1, H2A, H2B, H3 & H4
 These small proteins are
positively charged at
physiologic PH as a
result of their high
content of lysine and
arginine so they form
ionic bonds with
negatively charged
phosphate group in DNA
Functions of Histones
1- Compacting DNA strands: the compacting
molecule is 40,000 times shorter than an
unpacked molecule
2- Chromatin regulation: modified histone have
important role in biological processes as:
Gene regulation
DNA repair
Chromosome condensation
3- Conserved packing material of DNA:
important in chromosome stabilization and
gene expression
1-Formation of nucleosomes
 Nucleosome is formed of a histone core of 8 molecules
of histones, 2 H2A, 2 H2B, 2 H3, & 2 H4, around which a
segment of DNA double helix is wrapped nearly twice left
handed super helical turns
 Organization of the DNA double strand in nucleosomes
make it to look like beads in a string, the 10 nm fiber
Linker DNA
Neighboring nucleosomes are joined by Linker stretch
of DNA (approximately 50 base pairs), & is covered by 1
molecule of H1, thus completing 2 DNA turn
H1 is the most tissue-specific & species specific of the
histone. It facilitates the packing of nucleosomes into
more compact structures
2-higher level of organization
Nucleosomes can be packed more tightly to form a
polynucleosome (6-7 Nucleosomes per turn) to form
30nm fiber also called nucleofilament which look like
solenoid (cylindrical coil)
The 30 nm fiber is
organized into loops
that are anchored by a
nuclear scaffold
containing several
proteins
(scaffold proteins e.g
topoisomerase II) to give
700 nm structure
Additional levels of
organization lead to the
final chromosomal
structure (1400 nm)
2 nm
Levels of DNA
packaging
1- 2 nm double
stranded
molecule
2- 10 nm
nucleosomes
3- 30 nm fiber
Organization
around a
central scaffold
10 nm
30 nm
300 nm
700 nm
1400 nm
Chromosomes
 During metaphase, DNA can
be seen under microscope
as super packed
chromosomes, where
identical sister chromatides
are connected at the
centromere (8,000 fold
shorter than primary B-form)
 In human, 23 pairs of
chromosomes are
found & numbered
according to their
length and position of
centromere
 In Somatic cells: genome is
diploid. Thus, each human
somatic cell contains 22
pairs of homologous
autosomal chromosomes & 2
sex chromosomes XX in
female or XY in male.
 In gametes (ova, sperm):
genome is haploid. Thus the
human gametes contain 22
autosomal chromosomes
and one sex chromosome, X
in female gamete or Y in
male gamete
Gene & Genome
 Gene is the fundamental unit of hereditary
 It's a segment of DNA on a specific position (Locus) on
chromosome
 Each gene is a part of DNA sequences that contains
genetic information coding for synthesis of one
polypeptide (protein)
 Genome is the total number of genes within one mature
cell of an organism
 Only about 10% of the human DNA contains genes. The
remaining 90% of DNA are as important as regulatory and
identity functions
Types of genes
A) House keeping genes: these genes are essential for
cell life
They are integral parts of the cells e.g. hexokinase
gene that essential for glucose metabolism inside
every cell
B) Differential (specific function) genes: these are
genes that essential for performance of specific
functions and so differ in each organ e.g. genes
specific for liver functions will only be expressed in
the liver cells, genes for insulin will be active in beta
cells of pancreas only
Human Genome project (HGP)
 Is an international project aiming for
sequencing and localization of each
gene along the human genome
 started 1990 & the rough copy of
HGP was obtained June 2000
 Through this project the following
information can be obtained:
a) The function & site of each gene
along specific chromosomes
b) A genetic finger-print or a gene map
for each individual can be done through
which we can predict susceptibility or
resistance to various diseases
Flow of genetic information
 In almost all organism, the flow of genetic
information goes in one direction from the
stored gene code in DNA by transcription into
a message copy as mRNA that is then
translated into a protein that carry out the gene
function
DNA to DNA → Replication
DNA to RNA → Transcription
RNA to protein →Translation
Flow of genetic information
Retroviruses (RNA viruses as AIDS virus) are
viruses that have at their core RNA as the
genetic information not DNA
Therefore, the mechanism of flow of genetic
information is reversed i.e. from RNA into DNA
then into mRNA then protein
Questions