DNA replication,repair and mutation

1. DNA
By,
Vanitha M

2. Content
1. Introduction
2. The DNA is the material of inheritance
3. Replication
4.Repair
5.Genetic code
6. Mutation

3. DNA determines who we are

4. DNA determines who we are

5. DNA and behavior
DNA: our robotic self
Brain: our free self
….or?

6. The age of DNA
Medicine and Biotechnology

7. The function of DNA
1. Transmission of genetic information (inheritance):
- mediated by germ cells
2. Control of cell function: in each cell
(in embryogenesis and adult body)
1

8. The DNA
is the material of inheritanceAugust Weismann
or protein?
Chemical nature
The big question: DNA
Localization:
- In the nucleus
- Weismann (1890): materials in the nucleus controls the cellfunction
- In the chromosomes
2

10. The DNA
is the material of inheritance
Stadler and Über:
Wavelength (nm)
Mutationefficiency
Absorption spectrum (DNS)
Absorption spectrum (protein)
max
max
The absorption spectrum of DNA and the effective spectrum of mutagenesis coincide (260 nm)
- the maximal absorption of proteins is at 280 nm
Mutagenezis
3

11. The DNA
is the material of inheritance
Griffith: genetic transformation of nonvirulent pneumococci
Frederick Griffith
4

12. The DNA
is the material of inheritance
Avery: genetic transformation by DNA
Oswald T. Avery
5

13. The DNA
is the material of inheritance
The Herschey and Chase experiment
Martha Chase Alfred Hershey
Bacteriophage T2
attaches to the
surface of abacterium
and injects its DNA.
Viral genes take over
the host’s machinery
and synthesizes new
viruses.
The bacterium bursts,
releasing about 200viruses.
6

14. The Tobacco mosaic virus (TMV) experiment:
The RNA
can also be the genetic material
7

15. The structure of DNA
8

16. Chargaff’s rule
A = T; G = C Contradicts to Leven’s tetranucleotide hypothesis (A=T=C=G)
Erwin Chargaff
The structure of DNA
9

17. Alexander Todd
Todd: phosphodiester bond – nucleotides form polymers
The structure of DNA
10

18. Alexander Todd
deoxyribose ribose
ester bond
phosphate
deoxyribose
base
3’
5’
3’
5’
Todd: phosphodiester bond – nucleotides form polymers
The structure of DNA
10

19. Alexander Todd
Todd: phosphodiester bond – nucleotides form polymers
The structure of DNA
Sugar-phosphate backbone
Bases
10

20. The structure of DNA
Rosalind Franklin
Franklin: X-Ray crystallography helped reveal the structure of DNA
11

21. The structure of DNA
James Watson FrancisCrick
DNA is a double helix
Model building
12

22. Base pairing in DNA is complementary
5′ end
TA pairs havetwo
hydrogen bonds.
CG pairs havethree
hydrogen bonds.
3′ end
The structure of DNA3′ end
James Watson FrancisCrick
12

23. X
H
N
N
N
N
H
N
H
A
O
O
H
H
N
H
H
H
T
N
O
H
N
N
N
G
N
H H
O
H
N
C
N
N
H H
H
deoxyribose
H
deoxyribose
deoxyribose
deoxyribose
The structure of DNA
thymine (T) adenine (A) cytosine (C) guanine (G)
H
N
13

24. James Watson FrancisCrick
Characteristics of the genetic material
and the DNA structure
(1) The genetic material stores an organism’s genetic information
- the combination of the bases can produce it
(2) The genetic material is capable for mutation
- changing of base pair sequences can produce it
(3) The genetic material is precisely replicated
- it is accomplished by the complementary base pairing
(one DNA strand contains the information of the other strand
14

25. Nobel Prize in Physiology or Medicine (1962)
J.D.Watson F.H.Crick M.H.F. Wilkins
What about R. Franklin?
15

26. Kornberg: in vitro DNA replication
Arthur Kornberg
3 subtances are needed :
(1) DNA polymerase (isolated by Kornberg)
(2) dNTPs: dATP, dCTP, dGTP, dTTP
(3) DNA template
DNA replication
16

27. DNA replication
The three possible models for DNA replication
Conservative
Semiconservative
Dispersive
Matthew Meselson Frank Stahl
17

28. DNA replication
Meselson and Stahl’s experiment: semiconservative DNA replication
N15
N14
Heavy N
Light N
17

29. DNA replication
The direction of new strand synthesis is 5’  3’
18

30. DNA replication
RNA primer is needed for chain initiation
19

31. DNA replication
leading strand
parent strand
leadingstrand
lagging strand
leading strand
lagging strand
Okazaki fragments
20

32. DNA replication
21

33. Replication

39. Repair
22

40. Genetic code
The genetic code is composed of triplets
Code: in DNA
Codon: in mRNA
Anticodon: in tRNA
--------
Start codon: AUG
Stop codons: UAA, UAG, UGA
(1) The genetic code is composed of triplets: one triplet encode one amino acid
(2) The genetic code is redundant: many amino acids are encoded by more than one triplets
(3) The genetic code is „comma-free”: the triplets are not isolated units
(4) The genetic code is universal: every living being is descended from a single common ancestor
Few exception: mitochondria, chloroplasts, protistas - in 1-1codons
23

41. Mutation
alterations of the nucleotide sequence
Somatic mutations occur in somatic (body) cells. Mutation is passed to daughter cells,
but not to sexually produced offspring
Germ line mutations occur in cells that produce gametes. Can be passed to next generation
----------
Point mutations: change in a single base pair—loss, gain, or substitution of a base (can
result from replication and proofreading errors, or from environmental mutagens)
Chromosomal mutations: change in segments of DNA—loss, duplication, or rearrangement
----------
Spontaneous mutations
- occur with no outside influence. Several mechanisms:
Induced mutation
- due to an outside agent, a mutagen
24

42. Silent mutation
- no change in amino acid sequence
25

43. Missense mutation
- base substitution results in amino acid substitution
26

44. - Sickle allele for human β-globin is a missense mutation: glutamic acid  valine at 6th position
- Individuals that are homozygous have sickle-cell disease
Missense mutation
27

45. - base substitution results in a stop codon
Nonsense mutation
28

46. Frame-shift mutation
- single bases inserted or deleted—usually leads to nonfunctional proteins
29

47. Deletions
Chromosomal mutations
Translocations
Insertions
30

48. Mutation provides the raw material for evolution in the form of genetic diversity.
Mutations can harm the organism, or be neutral.
Occasionally, a mutation can improve an organism’s adaptation to its environment,
or become favorable as conditions change.
Mutation
31