DNA repair systems fix damage to DNA to prevent mutations. The main repair pathways are mismatch repair, base excision repair, nucleotide excision repair, and double strand break repair. Defects in repair genes can lead to cancers like xeroderma pigmentosa. The genetic code translates DNA into protein via mRNA. It is degenerate, unambiguous, and universal, with some variation between organisms. Mutations are changes to DNA that can be point mutations or frameshift mutations, and can have effects like causing disease or cancer.

1. DNA REPAIR, GENETIC CODE
& Translation
DR. Vishnu Kumar
PROFESSOR & HEAD,
DEPT.OF BIOCHEMISTRY
MPTMC, SIDDHARTH NAGAR
COMPETENCY NUMBER BI 7.2

2. LEARNING OBJECTIVES
After completion of this lecture learner
should be able to define/ describe:
• DNA Repair
• Genetic Code
• Mutation

3. DNA Repair
• The most serious outcome of DNA
damage is mutation i.e. permanent and
heritable change in the genome which
may cause cancer, genetic disease.
• In addition to proof reading activity an
elaborate system of DNA repair exists in
the body.

4. Types of DNA repair
• 1) Mismatch repair.
• 2) Base excision repair
• 3) Nucleotide excision repair.
• 4) Double strand break repair.

5. Mismatch repair
• These are rare mistakes left over even
after proof reading, e.g. C could be
present opposite A.
• The repairing system must distinguish
between the template strand and the
new strand containing the wrong base.
This is accomplished by tagging the
template strand with methyl group (
CH3).
• Three proteins Mut S, MutL and Mut H
are needed for strand recognition.

7. Mismatch repair
• DAM methylase methylates the
template strand.
• An endonuclease will cut the strand
near the defect.
• An exonuclease will digest the strand
removing the faulty sequence.
• The gap is filled up by DNAP III, SSB,
helicase and ligase.

8. Base excision repair
• Spontaneous, chemical, radiation or
heat may damage a single base, e.g.
• Deamination of adenine to
hypoxanthine.
• Guanine to 6 methyl guanine.
• Uracil to 5 bromo uracil.
• Purine to amino purine.

9. • There is a class of enzyme called DNA
glycosylase that removes the affected
base. This creates an apurinic or
apyrimidinic site ( AP site ).
• AP endonuclease cuts the strand
containing the defective site.
• Proper base is replaced by DNA
polymerase 1 ( DNAPβ in eukaryotes.)
• DNA ligase causes final ligation.
Base excision repair

11. Nucleotide excision repair
• Chemicals, radiation or heat may
damage a segment of DNA up to 30
bases.
• The enzyme is ABC exonuclease.
• The enzyme hydrolyzes two phospho
diester bonds containing the defect.
• Synthesis of new strand by DNAP1 ( β
in eukaryotes).
• Final joining by DNA ligase.

13. Double strand break repair
• May occur by ionising radiation, chemo
therapeutic agents.
• Two proteins are involved KU, and DNA
PK which bind to the free ends and
allow approximation of two ends.
• Unwinding of the ends by helicase
activity of KU. Unwound approximated
ends form base pairs, the extra tails are
removed by exonuclease.
.

14. DNA repair and Cancer
• Human cancer develops when certain
genes that regulate normal cell division
(tumor suppressor gene or proto
oncogene) fail or altered.
• Cells may grow out of control and form
a tumor.
• Defects in the genes encoding the
proteins of different repair systems
have been linked to human cancer.

15. Xeroderma pigmentosa
• Defective nucleotide excision repair.
• UV light  damaged DNA. not
repaired due to defective NE repair 
replication of damaged DNA 
daughter DNA with mutation  mutated
DNA mediates cancer by activation of
proto oncogens multiple skin cancer.

16. Other cancers
• HNPCC  defective mismatch repair
• Cockayne’s syndrome  defective NE
repair.
• Ataxia telangiectasia  defect in
double strand break repair.
• Fanconi’s anemia  lethal aplastic
anemia due to defective double strand
break repair.

17. Genetic code
• Genetic information is stored in the
chromosome and transmitted to
daughter cells through replication. It
is expressed to RNA through
transcription.
• From the mRNA genetic information
is translated to polypeptides.
• the flow of information from DNA 
RNA  protein is called Central
Dogma of Molecular Biology.

19. Genetic code
Definition The set of triplet code
words in DNA or mRNA coding for
amino acids of protein. This is the
dictionary that gives correspondence
between a sequence of nucleotide
bases and a sequence of amino acids
in a protein. Each individual word in the
code is composed 3 nucleotides. These
genetic words are called codons.

21. Genetic code
• Altogether there are 64 codons of
which 61 codons code for 20 amino
acids in a protein. 3 codons act as
termination signal.
• 61 codons coding for amino acids are
called sense codons and the rest {UAG
(amber), UGA (opal) and UAA (ochre)}
are called nonsense codons.

24. Characteristics of genetic code
• Degenerate.
• Unambiguous.
• Non overlapping.
• Non punctuated.
• Universal.

25. Degeneracy
• This means multiple codons code for a
single amino acid. There are six codons
for serine, four for glycine and one for
methionine.
• AUG for methionine.
• GGA, GGC, GGG and GGG for glycine.

26. Unambiguity
• One specific codon codes for only one
specific amino acid.
• For example phenylalanine is coded
by both UUU and UUC but UUU will
code only for phenylalanine.
• So given a specific codon only a
specific amino acid will come although
given a specific amino acid, more than
one codon may be called.

27. Non overlapping & non
punctuation
• Non overlapping codons are
consecutive. They are read one after
another in a continuous manner.
• Non punctuation no comma between
two codons.

28. Universal
• Until recently the genetic code was
thought to be universal that means one
specific codon will code for one
specific amino acid in all the
organisms.
• Recently it has been shown that four
codons behave differently in cytoplasm
and mitochondria of the same cell. For
example UGA codes for termination
codon in cytoplasm and tryptophan in
mitochondria

29. Wobble
• The degeneracy of genetic code
resides mostly in the last base of the
codon, suggesting that the base pairing
between the last nucleotide of the
codon and the corresponding
nucleotide in the anticodon is not strict
and less strong. This phenomenon is
called Wobble.

30. Example of wobble
• The two codons for arginine AGA and
AGG can bind to the same anticodon
having uracil at the 5’ end. Similarly
three codons for glycine GGC, GGU,
and GGA can form base pair with the
same anticodon CCI.

31. Mutation
• Definition. Permanent and heritable
change in the genome which will
appear in the daughter DNA , after
replication, in the RNA after
transcription and in the protein after
translation.
• Types 1) Point mutation
2) Frame shift mutation.

32. Point Mutation
• Definition. single base alteration in
the gene.
• Classification.
• 2 classifications.
1) transition and transversion.
2) silent mutation, nonsense mutation
and missense mutation.

33. Transition & Transversion
• Transition  when one purine base is
replaced by another purine base.
• for example-- adenine guanine and
vice versa.
• Transversion purine is replaced by
pyrimidine.
• For example -- A  C, A  T, GC,
GT and vice versa.
•

34. Classification (2)
Silent mutation  The codon containing
the changed base may code for the
same amino acid. For example if
serine codon UCA is changed to UCU,
it still codes for serine. So there will be
no change in the protein product.
• Other examples  AGG and AGA both
code for arginine

35. Non sense mutation
• The codon containing the changed base may
become a termination codon.
• For example if serine codon UCA is given a
different 2nd base ( to become UAA) the new
codon becomes a termination codon which
causes premature termination of protein
synthesis at that point.
• Example  β thalassemia in which β chain of
hemoglobin is prematurely terminated.

36. Missense mutation
• The codon containing the changed
base may code for a different amino
acid, for example if the serine codon
UCA is given a different 1st base (to
become CCA ), it will code for a
different amino acid in this case
proline. This substitution of an
incorrect amino acid is called missense
mutation. Example  sickle cell
anemia.

37. Frame shift mutation
• The deletion or addition of a single
nucleotide in the coding strand of a gene
results in an altered reading frame in the
mRNA. When the mRNA is translated to
protein the machinery does not recognize
that a base is missing or extra since there is
no punctuation in the reading frame. Thus
three will be major alteration in the sequence
of amino acids distal to the deletion or
addition.

38. Example of mutation
• Point mutation ( missense)  sickle
cell anemia.
• Point mutation ( nonsense)  α and β
thalassemias.
• Frame shift mutation  thalassemias

39. Effects of mutation
• Lethal effect  if the mutation is
incompatible to the life. For example 
β-thalassemia major.
• Carcinogenic effect mutation may
result in uncontrolled cell division
leading to cancer.
• Disease  sickle cell anemia ,
thalassemia.