DNA Damage and Repair

DNA DAMAGE & REPAIR
INTRODUCTION:
Genetic variations are important for evolution but the

survival of the individual demands genetic stability.
Maintaining genetic stability
requires an extremely accurate mechanism for replicating DNA
and
mechanism for repairing the many accidental lesions
that occur continually in DNA.
Most such changes are temporary because they are
immediately
corrected by a set of processes that are collectively called as
DNA
repair.
CONTENTS:
• Double helical structure of DNA

• DNA damage
• Sources of DNA damage
• Causes of DNA damage
• Consequence of DNA damage
• DNA repair
• Direct repair
• Excision repair
• Mismatch repair
• Recombinational repair
• References
DOUBLE HELICAL STRUCTURE OF DNA:
DNA DAMAGE:
DNA damage is the alteration in the chemical structure

of DNA, such as a break in a strand of DNA, a base
missing from the backbone of DNA, a chemically
changed base.
Damage to DNA that occurs naturally can result from
metabolic or hydrolytic processes.
SOURCES OF DNA DAMAGE:
• Endogenous damage:
It includes damage from within the cell.
It also includes replication errors.
Example: Attack by reactive oxygen species produced from normal metabolic byproducts.
• Exogenous damage:
It includes damage caused by external agents.
Examples: 1.UV, X rays and gamma rays.
2.Plants of comfrey species.
3.Viruses.
CAUSES OF DNA DAMAGE:
• UV Rays:
Random photons of ultraviolet light induce aberrant bonding between
neighbouring pyrimidines(thymine and cytosine) bases on the same strand of
DNA. This will prevent the replication.
CONTD…
• Alkylating agents:
Methyl and ethyl group added to DNA bases alters the structure of DNA.
• Deamination:
An amino group of cytosine is removed and the base becomes uracil.
An amino group of adenine or guanine is removed and the base becomes
hyoxanthine.
CONTD…
• Depurination:
The base is simply ripped out of the DNA molecule leaving a gap(like a missing tooth).
CONSEQUENCES OF DNA DAMAGE:
• Leads to genome instability.

• Increased cancer risk.
• Accelerated ageing.
• Neurodegenerative diseases.
DNA REPAIR :
• DNA repair refers to the number of processes by which a

cell identifies and corrects damage to the DNA molecules
that encode its genome.
• Depending on the type of damage inflicted on DNA‘s

double helical structure, a variety of repair strategies
have evolved to restore lost information.
TYPES OF DNA REPAIR MECHANISMS:
1. Direct reversal
2. Excision repair
a)Base excision repair
b)Nucleotide excision
repair
3. Mismatch repair
4. Recombinational repair
DIRECT REPAIR:
• This system act directly on damaged nucleotides and

convert each one back to its original structure.But only a
few damaged nucleotides can be repaired directly.
• Pyrimidine dimers are repaired by a light-dependent direct
system called photoreactivation.
DIRECT REPAIR:
EXCISION REPAIR:
• It involves excision of a segment of the polynucleotide

containing a damage site, followed by resynthesis of the
correct nucleotide sequence by a DNA polymerase.
• Excision → Resynthesis → Ligation.
• Excision repair is of two types:
a)Base excision repair
b) Nucleotide excision repair
BASE EXCISION REPAIR:
• BER repairs damage to a single base caused by oxidation,

alkylation, hydrolysis, or deamination.
• The damaged base is removed by a DNA glycosylase,

resynthesized by a DNA polymerase, and a DNA ligase
performs the final nick-sealing step.
BASE EXCISION REPAIR:
NUCLEOTIDE EXCISION REPAIR:
• Nucleotide excision
repair recognizes
bulky helix-distorting
lesions such as
pyrimidine dimers and
6,4 photoproducts and
treats them.
MISMATCH REPAIR:
• Mismatch repair corrects errors of DNA

replication and recombination that results in
mispaired but undamaged nucleotides.
RECOMBINATIONAL REPAIR:
• Recombinational repair requires the presence of an

identical or nearly identical squence to be used as a
template for repair of the break in the DNA strand.
• The enzymatic machinery responsible is nearly identical
to the machinery responsible for chromosomal crossover
during meiosis.
REPLICATIONAL REPAIR :
REFERENCES:
• Albert, B., Bray, DD., Lewis, J., Rafif M., Roberts, K, Walson, J.D.,
Molecular Biology of the Cell. Garland Publishing Company, Inc., New
York.
• Benjamin, Lewin, Gene VIII, Oxford University Press, U.K.
• http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002369.
• http://www.suit101.com/content/defects-in-dna-repair-and-resulting-
diseases-a137961

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DNA DAMAGE & REPAIR

Genetic variations are important for evolution but the

• Double helical structure of DNA

DNA damage is the alteration in the chemical structure

• Leads to genome instability.

• DNA repair refers to the number of processes by which a

• Depending on the type of damage inflicted on DNA‘s

• This system act directly on damaged nucleotides and

• It involves excision of a segment of the polynucleotide

• BER repairs damage to a single base caused by oxidation,

• The damaged base is removed by a DNA glycosylase,

• Mismatch repair corrects errors of DNA

• Recombinational repair requires the presence of an

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