Topic : DNA damage repair.
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Introduction
Each cell contains only one or two copies of its DNA, the
DNA sequence is highly protected from harm.
DNA is a relatively stable molecule, but Earth’s
natural environment is quite toxic, and damage to DNA
is inevitable.
DNA can also be altered by mistakes made during
its own replication or recombination.
Damage and sequence alterations to DNA are often
quickly repaired, but when they are not, the
DNA becomes permanently altered and harbors a
mutation.
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Mutations are changes in DNA sequence, and when
mutations occur in germ-line cells, these changes are
Co ntinue . .
A cancer cell has mutations that prevent cell
death, resulting in loss of cell cycle control and
unregulated cell division, which leads to
malignant tumors that can end the life of the
entire organism.
The cell has a limited amount of time to fix the
initial alteration and restore the DNA to its
normal sequence, before replication converts the
alteration into a mutation that will be passed on to
the next generation.
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Co ntinue . .
Mutation
Somatic mutations : occur in somatic cells and only
affect the individual in which the mutation arises.
Germ-line mutations: alter gametes and passed to the
next generation.
Mutations are quantified in two
1. ways:
Mutation rate = probability of a particular type of
mutation per unit time (or generation).
2. Mutation frequency = number of times a
particular mutation occurs in a population of cells or
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individuals.
Types of DNA
mutations
A mutation is a change in a DNA sequence
that is propagated through cellular generations.
Mutations can be as small as a single base pair or
can range from a few base pairs to thousands.
Mutations of one or a few base pairs usually
result from errors in replication or damaged
nucleotides.
10/04/2023 Mutation can have different effects on gene
A Point Mutation Can Alter One Amino Acid
A change in a single
base pair is often referred to
as a point mutation.
□ Point mutations fall into two
categories:
i. A transition mutation is the exchange
of a purine-pyrimidine base pair for
the other purine-pyrimidine base pair:
C≡G becomes T=A, or T=A becomes
C≡G.
ii. A transversion mutation is the
replacement of a purine-pyrimidine
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base pair with a pyrimidine-purine
base pair, or vice versa.
□Transition mutations are nearly 10 times
more frequent than transversions.
□A point mutation in the protein-coding region
of a gene can result in an altered protein with
partial or complete loss of function.
If the protein is central to cell viability, the
cell could die.
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Point mutations in a protein-coding region can
be classified by their effect on the protein
sequence.
The DNA sequence encoding a protein is read in
codons. Each codon corresponds to an amino acid .
A silent mutation is a nucleotide change that
produces a codon for the same amino acid. For
example, GAA and GAG both code for glutamate.
A missense mutation is a nucleotide change that results
in a different amino acid, such as a change from
glutamate (GAA) to glutamine (CAA).
A nonsense mutation changes the nucleotide
sequence so that instead of encoding an amino acid, the
triplet functions as a stop codon, terminating the protein.
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Small Insertion and Deletion Mutations Change
Protein Length
Another type of mutation is the gain or
loss of one or more base pairs.
i. Insertion mutations occur when one
or more base pairs are added to the
wild-type sequence.
ii. Deletion mutations are due to the loss
of one or more base pairs.
Insertion and deletion mutations
are collectively referred to as indels.
The DNA sequence from the start
codon to the stop codon is referred to
as a reading frame.
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Because nucleotides are decoded in
triplets, an indel mutation of only one or
two base pairs in the coding sequence of a
protein throws off the reading frame after
the mutation, resulting in a frameshift
mutation.
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Types of mutations in
ORFs 1- Nonsynonymous/missense
Basemutation
pair substitution results in substitution of
a different amino acid.
2- Nonsense mutation
Base pair substitution in a codo (an shorte
results polypeptide). n d r
stop
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Co ntinue . .
3- Neutral nonsynonymous
Base mutation
pair substitution results in substitution of
an amino acid with similar chemical properties
(protein function is not altered).
4- Synonymous/silent mutation
Base pair substitution results in the same
amino acid.
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Co
ntinue . .
5- Frameshift
mutations:
Deletions or insertions (not divisible
translation
by of
3) incorrect
result in amino acids, stops
codons (shorter polypeptides), or read-through of
stop codons (longer polypeptides).
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