DNA MUTATION
AND REPAIR
SANJNA SRIDHAR- B0120006
WHAT IS GENETIC MUTATION?
● A mutation is a change in the DNA sequence of an organism. Mutations can
result from errors in DNA replication during cell division, exposure to mutagens
or a viral infection.
● Germline mutations (that occur in eggs and sperm) can be passed on to
offspring, while somatic mutations (that occur in body cells) are not passed on
● The term “mutant” refers to a person who exhibits these heritable alterations. Mutations
usually produce recessive genes.
● Our cells have very sophisticated machinery for repairing mutations very quickly
and doesn’t cause any harm
WHEN DO GENETIC MUTATIONS HAPPEN?
• Genetic mutations occur during
cell division when your cells
divide and replicate. There are
two types of cell division:
1. MITOSIS: During mitosis, your
genes instruct your cells to split
into two by making a copy of
your chromosomes
2. MEIOSIS: During meiosis,
chromosomes copy themselves
with half the amount of
chromosomes as the original
(from 46 to 23)
TYPES OF MUTATIONS
● Two major types:
1. POINT MUTATIONS
2. FRAMESHIFT MUTATIONS
● Point mutations: The replacement of one base pair by another results in point
mutation.
● They are of two types:
● TRANSITIONS: In this case, a purine (or a pyrimidine) is replaced by another.
● TRANSVERSIONS: These are characterized by replacement of a purine by a
pyrimidine or vice versa.
Class of Type of Human
Description Disease(s) Linked
Mutation Mutation
POINT MUTATIONS
to This Mutation
One base is incorrectly
• Point Mutation, A.K.A substitution, is a added during
replication and replaces
type of genetic mutation where the Substitution the pair in the
corresponding position
Sickle-cell
anemia
nucleotide base is inserted, deleted, or on
the complementary stra
changed in the DNA or RNA of the nd
genome of an organism
One or more extra
1. SUBSTITUTION MUTATIONS: If the Point nucleotides are
inserted into One form of
mutation occurs by the substitution of a mutation Insertion replicating DNA, beta-thalassemia
often resulting in a
nucleotide in the genome of an organism. frameshift
2. INSERTION OR DELETION MUTATION One or more
nucleotides is "skipped"
Deletion during replication or
otherwise excised, often
Cystic fibrosis
resulting in a frameshift
SUBSTITUTION MUTATIONS
It is further subdivided into three types:
1. Silent mutation
2. Mis-sense mutation
3. Nonsense mutation
FRAME SHIFT MUTATION
● Insertions or deletions of nucleotides in the coding region resulting in an altered
sequence of amino acids at the translation of the codons are known
as frameshift mutations.
● They result in phenotypic changes, for instance, the production of an altered
protein.
TYPES OF FRAMESHIFT MUTATIONS:
● Deletion frameshift mutation, wherein one or more nucleotides are deleted in
a nucleic acid, resulting in the alteration of the reading frame
● This mutation is also referred to as (+)1 frameshift mutation.
● Insertion frameshift mutation, wherein one or more nucleotides are added to
the base sequence of the nucleic acid, which results in the change in the reading
frame.
● This mutation is also referred to as (-)1 frameshift mutation.
The result of these
mutation can cause:
CAUSES OF MUTATION
• The mutation is caused due to the following reasons:
1. INTERNAL CAUSES: Most of the mutations occur
when the DNA fails to copy accurately. All these
mutations lead to evolution. During cell division, the
DNA makes a copy of its own. Sometimes, the copy
of the DNA is not perfect and this slight difference
from the original DNA is called a mutation.
2. EXTERNAL CAUSES: When the DNA is exposed to
certain chemicals or radiations, it causes the DNA to
break down. The ultraviolet radiations cause the
thymine dimers to break resulting in a mutated
DNA.
DNA REPAIR TYPES
DIRECT BASE
REVERSAL EXCISION
01 02
REPAIR REPAIR
NUCLEOTI
MISMATC
DE 03 04
H REPAIR
EXCISION
REPAIR
DNA REPAIR TYPES
◦ Various pathways exist for DNA repair. These include direct reversal, excision repair,
mismatch repair, and repair of DNA breaks.
1. DIRECT REVERSAL REPAIR :
• A DNA repair mechanism that directly fixes specific types of DNA damage without the
need for excision or replacement.
• Two examples of DNA damage that can be reversed are UV-induced lesions and
alkylated bases.
• UV-induced lesions, caused by UV light, can be reversed through a process called
photoreactivation, which uses visible light energy to break the damaged DNA
structure, restoring the original pyrimidine bases.
• Alkylated bases can be reversed by enzymes such as O6-alkylguanine-DNA alkyl
transferase (AGT) and AlkB-related dioxygenases, which removes or modifies the alkyl
group, respectively.
2. BASE EXCISION REPAIR :
• A DNA repair mechanism that removes and replaces damaged bases.
• It involves the action of various DNA glycosylases such as 8-oxoguanine DNA glycosylase
(OGG1). These enzymes recognize and remove damaged bases.
• BER includes both short patch repair, where an abasic site is processed and filled by specific
enzymes, and long patch repair, where gaps are tailored and DNA synthesis occurs followed
by ligation.
• One example of BER is the repair of uracil-containing DNA. In this process, a DNA
glycosylase recognizes and removes the uracil base, creating a gap in the DNA called AP site.
The gap is then cleaved by an enzyme called AP endonuclease. After that, the remaining
sugar is removed, and the gap is filled using DNA polymerase and sealed with ligase.
3. NUCLEOTIDE EXCISION REPAIR:
• Nucleotide excision repair (NER) deals with bulky adducts and cross-linking
lesions caused by UV radiation or chemical exposure.
• NER removes a fragment of nucleotides containing the damaged lesion and
synthesizes a new DNA strand using the undamaged strand as a template.
NER CONSISTS OF TWO PATHWAYS:
• Global Genome NER (GG-NER) repairs bulky damages throughout the entire
genome, including regions that are not actively transcribed.
• Transcription-Coupled NER (TC-NER) repairs damage that occurs on the
transcribed DNA strand.
• Mutations in NER pathway genes can lead to disorders such as xeroderma
pigmentosum (XP) and certain other neurodegenerative conditions.
4. MISMATCH REPAIR:
• It repairs base mismatches and insertion-deletion loops that occur during
replication. Most of these errors are fixed by the proofreading activity of DNA
polymerase during replication, but some may be missed and need to be
corrected later.
THE MMR PATHWAY INVOLVES THREE STEPS:
1.Recognition of mismatches
2.Degradation of the error-containing strand
3.Synthesis of the correct DNA sequence
• Mutations in MMR genes can lead to Lynch syndrome, a hereditary condition
associated with an increased risk of colon, ovarian, and other cancers.
