DNA can be damaged through various means, both endogenous and exogenous. Endogenous damage occurs as a result of normal cellular processes and metabolism, and includes deamination of bases, resulting in base mismatches during replication. Exogenous factors include physical agents like radiation which can cause base dimerization, and chemical agents that induce adducts and strand breaks. Unrepaired damage can lead to mutations being passed on if they affect the coding regions of genes. The cell has multiple repair pathways to prevent mutations from occurring and to maintain genomic integrity.

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DNA DAMAGE (sadhna Pandey)
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• DNA is a polymer
• synthesis begins with a pre-existing
single DNA strand
• The DNA of the cell is the single
blueprint that contains all the information
to make a new copy of itself and any
other polymer molecule in the cell.
• genetic information coded in DNA could
be recovered from its single strand.
• The preservation house of the genes
• Information in DNA is dependent on the
accuracy of its COPYING mechanism and
efficiency of REPAIR Process
THE DNA FACTS

4. DEFINITIONS of DNA DAMAGE
Damage to DNA consists of any change that
introduces a deviation from the usual
doublehelical structure. (Benjamin Lewin –
GENES) "Drug- or radiaon-induced injuries in DNA
that introduce deviaons from its normal
double-helical conformaon. These changes
include structural distorons which interfere
with replicaon and transcripon, as well as
point mutaons which disrupt base pairs and
exert damaging effects on future generaons
through changes in DNA sequence".
"Any modificaon in the physical and/or chemical structure of DNA
resuting in an altered DNA molecule which is different from the original
DNA molecule with regard to its physical,chemical and/or structural
properetis".
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Estimated rates of DNA damage per
human cell per day

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Mutation is rare because
of repair”

7. Classificaon of factors causing DNA damage
A on the basis of origin
factors of exogenous origin -. environmental
factors)
factors of endogenous origin- Produced by cell
metabolism
DNA damaging agents may cause
Direct effect on DNA
(base modifying aagents) or
induce structural changes.
(triple-strand structures in DNA responsible
for for copying errors during replication)
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8. Classificaon of factors causing DNA damage
A on the basis of origin
Factors of exogenous and endogenous origin
B Nature of DNA damaging agents (physical
and chemical agents)
C Factors causing alterations in the
informaon content of DNA
D factors causing structural alteration) .
E Cytotoxic and genotoxic agents
F Mutagens and teratogens
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PHYSICAL AGENTS:
short-wavelength electromagnec energy
(ultraviolet (UV) radiaon and ionising radiaon.)
CHEMICAL AGENTS :
alkylating agents, oxidising agents, chemicals
creating DNA-DNA orDNA-protein crosslinks
Fffects : Structure
properties
Introduce bulky Adducts
B Nature
of
DNA damaging agents

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Conversion of one base to another,
producing a mismatch Deaminaon of
nitrogenous bases
Uracil pairs more efficiently with A than with G,
(mismatch.)
In the next round of DNA replication, this will
result in a substituon of a C:G pair with an A:T
pair.
1
Damages of
Endogenous
origin

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2 . Deaminaon of adenine to hypoxanthine.
pairs more readily with C
than with T.

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Cytosine
methylaon on
posion 5.
Modificaon of bases
thymine pairs with
adenine,
substuting a C:G
pair with a T:A pair
in the next round
of replication.

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i) Mismatched bases in DNA cause alterati
ons of the informaon content of DNA.
Resulting in substitutions of amino acids;
ii) Altered protein mismatches may introduce a
premature stop signal in mRNA, resulting in
truncated and/or unstable protein or no protein.
consequences

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Loss of nitrogenous bases due to hydrolysis
loss of nitrogenous bases is DNA depurintiaon, a
common type of DNA damage (5x10 - 1x10 mes per
genome per day inhuman cells )
DNA depurinaon occurs much faster than depyrimidinaon.
Loss of nitrogenous bases in DNA is strongly dependent on
the temperature
Loss of nitrogenous bases results in abasic sites in DNA.
This, in turn, may promote strand
breakage and/or mispairing

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Alkylation (methylation) of nitrogenous bases
alkylation affects a nitrogen or an oxygen atom in
a nitrogenous base in DNA,
Results in modified bases - 5-methylcytosine, 7-
methylguanine, 1-methyladenine, etc
Alkylated bases may show different pairing
properties
O6-alkylguanine and O4-
alkylthymine tend to pair with

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Alkylation (methylation) of nitrogenous bases
Cosequences
Disorders of methylation may affect somatic
cells (cancer)/ germline.
inherited human diseases Rett syndrome,

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.4. Oxidaon of nitrogenous bases
Oxidaon of nitrogenous bases affects both purine
pyrimidines
Purine base oxidation results in 8-oxopurines
pyrimidines into thymine glycol, uracil glycol, 5-
hydroxycytosine and 5-hydroxyuracil
Base oxidation in DNA may result in strand breaks

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.5. DNA breaks of endogenous origin
Single-strand breaks (SSBs) break
in phosphodiester bond between two
adjacent deoxyribose residues in the
backbone of DNA.
most common instances of DNA
damage.
Double-strand breaks (DSBs) are
less common and are lethal.

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. Damage of exogenous origin
B1 Dimerisation
B2 Tautomeric isomerism of nitrogenous
bases (keto-enol and amino-imino)
B3. Formation of bulky adducts in DNA
B

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. Damage of exogenous origin
1. Dimerisation
due to electromagnec radiaon in the UV
rangeThe type of UV-induced damage to
DNA is dependent on the wavelength of the
UV.
Dimers are most oen caused by high-
energy, short-wavelength UV in the range of
100-300nm
Dimerisaon may occur between bases
belonging to the same strand of DNA or
between bases from different DNA strands
B

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Formation of
Dimers

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B2 Tautomeric isomerism of nitrogenous
bases (keto-enol and amino-imino)
thymine in its enolic from preferentially pairs
with guanine and not adenine. Guanine-enol
pairs with thymine.

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B3 Formation of bulky adducts
bulky adducts in dividing cell normally cause
replication arrest . Aromatic compounds and,
aromatic hydrocarbons (PAH) are among
potent adduct-forming environmental agents.
benzopyrene diol epoxide,
benzopyrene (a compound of tobacco
smoke). metabolites cause mutation in TP53
gene, (smoking-related
lung cancers

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B3 Formation of bulky adducts
bulky adducts in dividing cell normally cause
replication arrest . Aromatic compounds and,
aromatic hydrocarbons (PAH) are among
potent adduct-forming environmental agents.
benzopyrene diol epoxide,
benzopyrene (a compound of tobacco
smoke). metabolites cause mutation in TP53
gene, (smoking-related
lung cancers

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.5. DNA breaks of endogenous origin
Single-strand breaks (SSBs) break
in phosphodiester bond between two
adjacent deoxyribose residues in the
backbone of DNA.
most common instances of DNA
damage.
Double-strand breaks (DSBs) are
less common and are lethal.

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types of DNA damage:
Spontaneous loss of bases
Alkylation of bases
Oxidation of bases
Formation of dimers
DNA strand breaks: Natural
cellular processes, exposure
to radiation (cosmic, medical
e.g. X-rays, radiation
therapy) and some forms of
chemotherapy

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