In contrast to DNA damage, a mutation is a change in the base sequence of the DNA. A mutation cannot be recognized by enzymes once the base change is present in both DNA strands, and thus a mutation cannot be repaired. At the cellular level, mutations can cause alterations in protein function and regulation.

1. DNA MUTATION
AND
ITS REPAIR
PRESENTED BY
MD ALTAMASH AHMAD
PHARM. D 1ST YEAR
1850951001

2.  DNA is deoxyribonucleic acid, and is
contained in your body's cells
 It is a double, long chain of
molecules called nucleotides
 The DNA itself makes up
chromosomes

3. Basic Terminologies
Nucleotide :
 A nucleotide is an organic molecule that is the building block of DNA and
RNA
A nucleotide is made up of three parts: a phosphate group, a 5-carbon
sugar, and a nitrogenous base.
The four nitrogenous bases in DNA are adenine, cytosine, guanine, and
thymine. RNA contains uracil, instead of thymine.
Codon :
A series of three nucleotides within the DNA is known as a codon
Each codon codes for a specific amino acid resulting to synthesis of a
specific protein

4. Nitrogenous bases

6. What does DNA Mutation means?
 DNA mutation is permanent change in the nucleotide sequence
of DNA.
 It may arise due to errors in replication and/or recombination,
chemical damage or radiation to the particular DNA.

7. Types of DNA mutation
There are three types of DNA Mutations:
1. Base substitutions
2. Deletions
3. Insertions

8. 1. Base Substitutions
Single base substitutions are called point
mutations.
Eg: Glu --> Val which causes sickle-cell disease
Point mutations are the most common type of
mutation and there are two types.
(A) Transition: this occurs when a purine is substituted with
another purine or when a pyrimidine is substituted with
another pyrimidine.
(B) Transversion: when a purine is substituted for a
pyrimidine or a pyrimidine replaces a purine.

10. Point mutations that occur in DNA sequences encoding
proteins are:
• Silent
• Missense
• Nonsense

11. 2. Deletions
In Deletion, one or more base pairs are lost from the DNA resulting in frameshift
of the sequence. If one or two bases are deleted the translational frame is
altered resulting in a distorted message and non-functional product. A deletion
of three or more bases leave the reading frame intact. A deletion of one or more
codons results in a protein missing one or more amino acids. This may be
deleterious or not.

12. 3. Insertions
The insertion of additional base pairs may lead to frameshifts depending on
whether or not multiples of three base pairs are inserted. Combinations of
insertions and deletions leading to a variety of outcomes are also
possible.

13. Causes of Mutations:
1. Errors in DNA Replication
On very, very rare occasions DNA polymerase will incorporate a non-complementary
base into the daughter strand. During the next round of replication the
misincorporated base would lead to a mutation.
2. Errors in DNA Recombination
DNA often rearranges itself by a process called recombination which proceeds via a
variety of mechanisms. Occasionally DNA is lost during replication leading to a
mutation.
3. Chemical Damage to DNA
Many chemotherapeutic drugs and intercalating agent drugs function by damaging
DNA.
4. Radiation
Gamma rays, X-rays, even UV light can interact with compounds in the cell generating
free radicals which cause chemical damage to DNA.

14. DNA Repair Mechanisms
1. DNA polymerase proofreading - 3’-5’ exonuclease activity corrects errors during
the process of replication.

15. 2. Photoreactivation (also called light repair) - photolyase enzyme is activated
by UV light (320-370 nm) and splits abnormal base dimers apart.

16. 3. Demethylating DNA repair enzymes - repair DNAs damaged by alkylation.

17. 4. Nucleotide excision repair (NER) - Damaged regions of DNA unwind and are
removed by specialized proteins; new DNA is synthesized by DNA polymerase.

18. 5. Methyl-directed mismatch repair - removes mismatched base regions not
corrected by DNA polymerase proofreading. Sites targeted for repair are
indicated in E. coli by the addition of a methyl (CH3) group at a GATC sequence.

19. Thank You
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