DNA DAMAGE AND REPAIR

-PRESENTED BY-
YEASMIN AKHTAR
ROLL NO- LS 20
DEPT. OF LIFESCIENCE AND BIOINFORMATICS
 INTRODUCTION

• DNA is the repository of genetic information.

• It gets damaged ten thousand of times per day.
• So maintaining the integrity of DNA molecule is crucial
to cells.
• Sometimes damages can occur spontaneously or as a
result of exposure to environmental agents such as
radiation , chemicals etc.
• To overcome the harmful effects of DNA damages cells
have various repair system to tolerate DNA damage and
Ensuring overall survival and functionality of cells.
 DNA DAMAGE

• DNA damage is any change to the chemical structure of DNA that can interfere
with its normal function.
• It may occur at the level of nucleotide bases , sugar phosphate backbone, or the
double stranded helix.
• DNA damages can cause changes in the chemical structure of genetic material
And prevents replication mechanism from functioning and perform properly.
 SOURCES OR AGENTS OF DNA
DAMAGE

ENDOGENOUS EXOGENOUS
• Replication error that occurs during DNA • UV radiation can form pyrimidine dimer where
replication, when incorrect nucleotide are two pyrimidine on the same DNA strand are
inserted opposite strand. joined together.

• Reactive Oxygen Species (ROS) are • Exogenous alkylating agents found in sources
like tobacco smoke and industrial activities reacts
produced during cellular processes can cause
with DNA and can cause mutagenic and
oxidative damage to DNA. carcinogenic damage.
• Alkylating agents are reactive compound that • Ionizing radiation comes from cosmic radiation
can add methyl or ethyl groups to DNA bases and medical treatment directly affects the DNA
leading to chemical modification. structure.
• Aromatic amines found in cigarette smoke, fuel,
coal , dyes and pesticides are also exogenous
source of DNA damage.
 TYPES OF DNA DAMAGES

DNA STRAND BREAK

• Occurs when one or both strand of DNA are interrupted.
▪️There are two types of DNA strand break –
• Single- strand Break : where one strand is cut
• Double –strand Break: where both strand are cut.
Alkylation of Bases
• Alkylating agents both endogenous and exogenous can modify DNA bases by
introducing alkyl group.
• Addition of alkyl group to specific bases (Guanine)
resulting in alkylation product such as
O6- methylguanine.
Oxidation of Bases
• This occurs due to the action of ROS which lead to the formation of lesions.
• The high reactive ROS such as (.OH) can
Cause oxidative damages to DNA bases.
 HYDROLYSIS OF DNA BASES
Deamination Depurination
• It is the removal of amino group from the • It is the loss of purine base from DNA
amino acid and converted into ammonia. strand.
• For Example: conversion of cytosine to • After depurination an apurinic site is
uracil , conversion of adenine to formed where the sugar phosphate
hypoxanthine and guanine to xanthine backbone remain and the sugar ring has
etc. hydroxyl group in place of purine.
Bulky Adduct Formation
• These are formed When certain chemicals like PAH and aromatic
Amines are covalently bind to DNA bases and disrupt DNA structure.

DNA Crosslinking
• It occurs when two nucleotide in DNA becomes covalently linked together.
• It can happen between same strand ( intrastrand) or between opposite strand
(inter stand)
 DNA REPAIR

• DNA repair is a collection of processes by which a cell identifies and correct

damages to DNA molecule that encodes it’s genome.
• It is a well known cellular defence mechanism responsible for maintaining the
genome integrity.
• This mechanism helps cells to cope with DNA damages.

Direct Damage Reversal Excision of DNA Damage

▪️Photoreactivation ▪️Base Excision

▪️Alkyltransferase Repair
• Types of DNA repair :
▪️Methylguanine ▪️Nucleotide
methyltransferase Excision Repair
▪️Mismatch
Repair
▪️Strand Break
Repair
 PHOTOREACTIVATION ALKYLTRANSFERASE
• It refers to the DNA repair system where • This mechanism repair alkylation
the re-exposure repairs the UV damaged damage to DNA bases.
DNA under visible light. • When an alkylating agent CH3 enters
• It is also called Light Repair. into DNA bases it breaks off the bond
between bases .
• A DNA helix become distorted and
pyrimidine dimers under UV light • Now the damaged is recognised by the
exposure. enzyme Alkyltransferase that transfer the
alkyl group from damaged base to a
• An enzyme photolyase ( FAD and MTHF)
cysteine residue in the enzyme.
Break the covalent bond between the
dimer.
 E X C I S I O N R E PA I R

BASE EXCISION REPAIR NUCLEOTIDE EXCISION REPAIR

• This mechanism repaired damage or modified bases • This mechanism repairs bulky lesions such as
pyrimidine dimers caused by UV radiation.
• It involves the removal of damaged bases by a DNA
glycosylase enzyme followed by endonuclease then • In E.coli the NER system require four key protein –
polymerase and then ligase. Urv A ,UrvB, UrvC and UrvD
• The enzyme Uracil DNA glycosylase remove uracil • These are important in repairing chemically
created by spontaneous deamination of cytosine in the damaged DNA
DNA.
• This Urv Protein recognises and remove a short
• An endonuclease removes a few bases.
segment of damaged DNA.
• The gap is filled by the action of DNA polymerase.
• DNA polymerase now filled the gap and seals the
• The strand is now re-joined by DNA ligase. gap by DNA ligase.
 MISMATCH REPAIR DOUBLE STRAND BREAK
• It correct mispaired bases including base mismatch, • It is the most cytotoxic DNA insult.
insertion and deletion.
• There are two mechanism by which the cells attempt to
• This repair system helps to identify DNA helix distortion repair a complete break in a DNA molecule.▪️
and get rid of replication error.
▪️Non-homologous End Joining: this requires protein that
• For the correction of mismatch bases (G and T) some recognises and bind to exposed end and bring them
proteins called Mut proteins are recruited. together for ligating. A protein called Ku is essential for
NHEJ.
• Mut-S detects the mismatch site and bind to it
▪️Homologous Recombination:
• Mut-S forms a complex with Mut-L.
• It is a precise repair pathway that requires a matching
• The formation of Mut-S and Mut-L complex recruits
DNA sequence as a template.
Mut-H to GATC sequence at hemiamylated site.
• It primarily uses sister chromatid for repair.
• A helicase and exonuclease are recruited to remove the
mismatch base pair. • Two of protein are used in in Homologous
Recombination are encoded by the genes BRCA1 and
• DNA pol III fills the gap.
BRCA 2 .
• New strand is sealed with
Ligase.
 CONCLUSION

• DNA damages leads to mutation.

• Mutation ultimately leads to the development of cancers.
• So DNA repair is important to maintain the integrity and overall functioning of
cells.
THANK YOU