The major scientific achievements of the 20th century was discovering that genetic information is coded in DNA, a polymeric molecule composed of four nucleotide units. DNA is organized into genes, which are the basic units of heredity. Knowledge of DNA and RNA structure and function is essential for understanding genetics, disease pathogenesis, and the genetic basis of disease. In 1953, Watson and Crick described the double helix structure of DNA based on Rosalind Franklin's X-ray crystallography photo, revealing how nucleotides on two intertwined DNA strands are paired through hydrogen bonds between complementary bases.
2. The major scientific achievements of the 20th century
is the discovery that genetic information is coded
along the length of a polymeric molecule composed
of only four types of monomeric units.
This polymeric molecule is DNA, the chemical basis of
heredity
DNA is organized into genes, the fundamental units
of genetic information.
The basic information pathway. ie,
Knowledge of the structure and function of nucleic
acids is essential in understanding genetics and many
aspects of pathophysiology as well as the genetic basis
of disease.
DNA RNA Protein
3. A HISTORY OF DNA
Discovery of the DNA double helix
Frederick Griffith –(1928) Discovers that a factor
in diseased bacteria can transform harmless
bacteria into deadly bacteria.
Maurice Wilkines – worked on the structure of
DNA.
Rosalind Franklin -(1952) - Worked out helical
structure of DNA by X-ray photo of DNA.
Watson and Crick - (1953)
described the DNA molecule from Franklin’s X-ray.
4. DNA is very long, thread like macromolecule
Mead up of a polymer of deoxyribonucleotide
Composed monomeric deoxynucleotide……
deoxyadenylate,
deoxycytidylate,
These monomeric units of DNA are held in
polymeric form by 3′,5′-phosphodiester bridges
constituting a single strand.
The informational content of DNA resides in
the sequence in which these monomers are
ordered.
Primary Structure of Nucleic Acids
(DNA)
thymidylate
deoxyguanylate
5. Formation of phosphodiester bond
Bases in DNA carry genetic information.
Sugar and phosphate perform structural role
6. Nucleotides Linked by Phosphodiester Bond
OH
PO4
2-
Phosphodiester bond
O-P=O-
O
O
5’
3’
PO4
2-
OH3’
5’
P
R
P
R
P
R
P
R
P
R
P
R
1
2
3’
5’
1
2
3
4
5
6
Akindofphospho-polysaccharides
7. The Notation for Nucleic Acids
P
R
B
3’
2’
5’
1’
A T C G A T C G
P OH
5’ 3’
5’ pApTpCpGpApTpCpG-OH 3’
5’ p-ATCGATCG-OH 3’
ATCGATCG
8. Erwin Chargaff(1940) quantitatively analyzed
DNA. He found that,
DNA had equal no of A & T and equal no of G &
C. this is known as Chargaff’s rule of molar
equivalence between the purines & pyrimidines in
DNA. ie.
A=T and G=C
Single stranded DNA & RNAs do not obey rule
Double stranded DNA & RNA(in some viruses)
satisfies chargaff’s rule.
Chargaff’s rule
10. Model they built of the structure of DNA
James
Watson
Francis
Crick
11. The Watson-Crick
DNA Double Helical Structure.
DNA consists two strands of nucleotides
that wind together in a double helix
(comparable to twisted ladder).
DNA is a right handed double helix.
These two DNA stands are antiparallel. The
two strands run in opposite directions.
The width of double helix is 20A°(2nm).
Each turn of the helix is 34A°(3.4nm) with
10 pairs of nucleotide, each pairs placed at
a distance of about 3.4 A°
12. The bases on the inside of the helix and
the sugar-phosphate backbones on the
outer side of the helix.
The two chains are held together by
hydrogen bonds between complementary
pairs of bases. ie.
A pairs with T by two hydrogen bonds.
G pairs with C by three hydrogen bonds.
DNA contains grooves of alternate size
called major grooves and minor grooves.
The sequence of the bases carries the
Genetic Information.
15. TYPES OF DNA
(different structural form of DNA)
DNA can exist in three structural forms
A-DNA
B-DNA (Watson-Crick model)
Z-DNA
Under physiological condition, DNA is
present in B form.
The characteristics of A,B and Z-DNA
are……..
16. CHARACTERISTICS OF A,B AND Z-DNA
Characteristics
property
A-DNA B-DNA Z-DNA
Shape Broadest Intermediate narrowest
Type of helix Right handed Right handed Left handed
Base pairs/turn 11 10 12
Rise / base pair 2.3 A° 3.4 A° 3.8 A°
Helix diameter 25.5 A° 23.7 A° 18.4 A°
Pitch/turn of
helix
25.3 A° 34 A° 45.6 A°
Major groove Narrow Wide Flat
Minor groove Very broad Narrow Very Narrow
19. Prokaryotic DNA
P.cell generally contains single chromosome.
Composed of double stranded circular DNA
Which contains over 4x106 base pairs.
The circular DNA is supercoiled and
attached to an RNA-protein core.eg E.coli.
20. Eukaryotic DNA
Eukaryotes contain over 1000 times the amount
of DNA found in prokaryotes.
Human haploid DNA contains 2.8x109 base
pairs.
This is distributed between 23 chromosomes.
A typical human cell contains 46 chromosomes
Whose total DNA is approx. 2 meter in length
The packing of DNA in a chromosome
represents 10,000 fold shortening of its length
3’-OH group of the sugar in one nucleotide forms an ester bond to phosphate group on 5’-carbon of the sugar of next nucleotide.
Resulting in a free 5’-phosphate group at one end & a free 3’-OH group at other end.
Is read from the free 5’end to 3’end using the letters of the bases.
This example reads
5’—A—C—G—T—3’.
雙螺旋 是一條雙股重複扭曲的螺旋鏈,其重複出現的扭曲單位如上圖所示;以常見的 B 型 DNA 而言,每 10.5 bp 形成一個扭曲單位,長度有 3.6 nm; 注意每一個扭曲單位中,DNA 的一股會交過另一股一次。 因為分子的扭曲並非對稱,因此分子表面會形成大小凹谷,這些凹谷對核酸與蛋白質的相互作用關係,有很大的貢獻。
同時因為磷酸脊骨露在外面,因此核酸的外側有相當大的負電聚集;若把 DNA 溶在純水裡,則兩股磷酸脊骨會互相排斥,造成 DNA 的兩股分開而變性沈澱,故 DNA 都要溶在含有離子的溶液中 (TE buffer)。