This document provides an overview of DNA repair mechanisms. It was authored by Arjun K B, a student at Kuvempu University's Sahyadri Science College Department of Biotechnology in Shimoga, India under the guidance of Dr. Prabhakar B T. The document contains an introduction to DNA structure and sources of DNA damage. It then discusses the importance of DNA repair in maintaining genomic integrity and preventing mutations that can lead to cancer. It proceeds to describe several DNA repair mechanisms in detail, including photoreactivation, base excision repair, mismatch repair, and SOS repair. The concluding section emphasizes the importance of an efficient DNA repair system for cell survival.

1. KUVEMPU UNIVERSITY
SAHYADRI SCIENCE COLLEGE
DEPARTMENT OF BIOTECNOLOGY
TOPIC:DNAREPAIR
UNDER THE GUIDENCE OF,
Dr. PRABHAKAR B T.
ASSISTANT PROFESSOR.
KUVEMPU UNIVERSITY,
SAHYADRI SCIENCE COLLEGE,
DEPARTMENT OF BIOTECNOLOGY.
SHIMOGGA..
FROM,
ARJUN K B.
1ST MSC
KUVEMPU UNIVERSITY,
SAHYADRI SCIENCE COLLEGE,
DEPARTMENT OF BIOTECNOLOGY,
SHIMOGGA.

2. CONTENTS:
1. INTRODUCTION.
2. SOURCES OF DNA DAMAGE.
3. WHY THE DNA REPAIR IS REQUIRED.
4. DNA REPAIR MECHANISM.
5. CONCLUSION.
6. REFERENCES.

3. DNA or deoxyribonucleic acid is a long
molecule that contains our unique genetic
code. Like a recipe book it holds the
instructions for making all the proteins in
our bodies.
• Your genome? is made of a chemical
called deoxyribonucleic acid, or DNA for
short.
• DNA contains four basic building blocks
or
‘bases: adenine (A), cytosine(C), guanin
e (G) and thymine(T).
• The order, or sequence, of these bases
form the instructions in the genome.
• DNA is a two-stranded molecule.
• DNA has a unique ‘double helix’ shape,
like a twisted ladder.
WHAT IS DNA ?
INTRODUCTION:
(fig0.1) STRUCTURE OF DNA

4. • Each strand is composed of long sequences of the four bases, A, C, G
and T.
• The bases on one strand of the DNA molecule pair together
with complementary? bases on the opposite strand of DNA to form the
‘rungs’ of the DNA ‘ladder’.
• The bases always pair together in the same way, A with T, C with G.
• Each base pair is joined together by hydrogen bonds.
• Each strand of DNA has a beginning and an end, called 5’ (five prime)
and 3’ (three prime) respectively.
• The two strands run in the opposite direction (antiparallel) to each
other so that one runs 5’ to 3’ and one runs 3’ to 5’, they are called the
sense strand and the antisense strand, respectively.
• The strands are separated during DNA replication.
• This double helix structure was first discovered by Francis Crick and
James Watson with the help of Rosalind Franklin and Maurice Wilkins.
• The human genome is made of 3.2 billion bases of DNA but other
organisms have different genome sizes.

5. SOURCES OF DAMAGE:
1. base modifications, such as alkylation
or deamination's which converts
cytosine, adenine and guanine to
uracil.
2. Replication errors and base conversions can
generate mismatch nucleotidepairs
3. Failures in normal DNA metabolism by
topoisomerases and nuclease or ionizing
radiation can generate single-strand and
double-strand breaks .
4. loss of a bases resulting in
apurinic/apyrimidinic (AP) sites (a basic
sites).
5. Photo damage by uv light can generate
pyrimidine dimers, such cyclobutane
pyrimidine dimers (CPDs)
6. Chemical agents and reactive oxygen species
(ROS) can modify bases .
(FIG0.2)SOURCES OF DAMAGE

6. • Consequently the DNA damage response
function will be deficient or impaired, and
damages will accumulate. Such DNA damages
can cause errors during DNA replication or
inaccurate repair, leading to mutations that
can give rise to cancer.
• At the cellular level, damaged DNA that is not
properly repaired can lead to genomic
instability, apoptosis, or senescence, which can
greatly affect the organism's development and
ageing process.
• The repair of damage to both DNA strands is particularly important in
maintaining genomic integrity. There are two main
mechanisms for repairing double strand breaks: homologous
recombination and classical no homologous end joining.
WHY THE DNA REPAIR IS REQUIRED?
(Fig0.3)

7. • Cyclobutane pyrimidine dimers can be
monomerized again by DNA photolyases
(photo reactivating enzymes) in the
presence of visible light. These enzymes
have prosthetic groups (see Topic B2) which
absorb blue light and transfer the energy to
the cyclobutane ring which is then cleaved.
The E. coli photolyase has two
chromospheres, N5,N10-
methenyltetrahydrofolate and reduced
flavin adenine dinucleotide (FADH). Photo
reactivation is specific for pyrimidine
dimers. It is an example of direct reversal of
a lesion and is error-free.
1.Photoreactivation:
DNA REPAIR MECHANISM:
(Fig0.4)
PHOTOREACTIVATION MECHANISM

8. • The E. coli photolyase has two chromospheres,
N5,N10-methenyltetrahydrofolate and reduced flavin
adenine dinucleotide (FADH). Photo reactivation is
specific for pyrimidine dimers. It is an example of
direct reversal of a lesion and is error-free.
(fig0.5) AZIZ SANCAR
NOBEL AWARDED FOR PHOTOREACTIVATION MECHANISM
IN2015 price share ½.

9. 2.BASE Excision repair :
• Base excision repair involves five basic steps,
beginning with the identification and removal of
the mutated base from the DNA helix by an
enzyme known as DNA glycosylase. Next, an
enzyme called AP (apurinic/apyrimidinic)
endonuclease makes an incision at the abasic
site, creating a break, or nick, in the strand of
DNA.
• The site is then “cleaned,” in which various
intermediates produced from the strand break
and other lingering chemicals are enzymatically
removed in preparation for repair synthesis.
• In the final two steps, one or more nucleotides
are synthesized to fill the gap, and the nick in the
DNA strand is sealed. (A nucleotide is a base
linked to a sugar and phosphate group, which
forms the backbone of DNA.)
(Fig0.6)
BASE EXCISION REPAIR MECHANISM

10. • DNA glycosylase has the ability to recognize a
number of different damaged bases. It is also
able to remove any DNA bases that are
cytotoxic (harmful to the cell) or that may
cause DNA polymerase (an enzyme involved in
DNA replication) to make errors. Some DNA
glycosylases have been shown to be
bifunctional, performing the aforementioned
activity as well as possessing lyase activity,
which enables it to cleave the DNA backbone
at the a basic site.
• A large number of DNA glycosylases are
known. Examples include uracil DNA
glycosylases, single-strand selective
monofunctional uracil-DNA glycosylase
(SMUG1), and thymine DNA glycosylase
(fig 0.7) TOMAS LINDAHL
NOBEL AWARDED FOR BASE EXCISION
REPAIR IN 2015 Price share 1/3.

11. 3.Mismatch repair :
This is a specialized form of excision repair that
deals with any base mispairs produced during
replication and that have escaped proofreading .
In a replicational mispair, the wrong base is in
the daughter strand. This system must, therefore,
have a way of distinguishing the parental and
daughter strands after the replication fork has
passed to ensure that the mismatched base is
removed only from the daughter strand. In
prokaryotes, certain adenine residues are
normally methylated in the sequence GATC on
both strands . Methylation of daughter strands
lags several minutes behind replication. Thus,
newly replicated DNA is hemimethylated the
parental strands are methylated but the daughter
strands are not, so they can be readily
distinguished.
(fig0.8) MISMATCH REPAIR MECHANISM

12. • The mismatched base pair is recognized and bound
by a complex of the MutS and MutL proteins which
then associates with the MutH endo-nuclease, which
specifically nicks the daughter strand at a nearby
GATC site. This nick initiates excision of a region
containing the wrong base. The discriminatory
mechanism in eukaryotes is not known, but mismatch
repair is clearly important in maintaining the overall
error rate of DNA replication and, there- fore, the
spontaneous mutation rate: hereditary nonpolyposis
carcinoma of the colon is caused by mutational loss
of one of the human mismatch repair enzymes.
Mismatch repair may also correct errors that arise
from sequence misalignments during meiotic
recombination in eukaryotes
(fig0.9) PAUL MODRICH
NOBEL AWARDED FOR MISMATCH
MECHANISM IN 2015 price share1/3.

13. 4.Hereditary repair defects:
• Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized
phenotypically by extreme sensitivity to sunlight and a high incidence of skin
tumors. XP sufferers are defective in the NER of bulky DNA damage, including
that caused by ultraviolet light. Defects in at least seven different genes can
cause XP, indicating the complexity of excision repair in mammalian cells.
Xeroderma pigmentosum variant (XP-V) is clinically very similar to classical XP
but cells from XP-V individuals can carry out normal NER. In this case, the defect
is in the gene encoding the translesion DNA polymerase h, which normally
inserts dAMP in an error-free fashion opposite the thymine residues in a
cyclobutane thymine dimer (see Topics F1 and F2). XP-V cells may, there- fore,
have to rely more heavily on alternative error-prone modes of translesion DNA
synthesis to maintain DNA integrity after radiation damage. Sufferers of
Cockayne syndrome are also sun-sensitive and defective in transcription-
coupled excision repair, but are not cancer-prone.

14. • Photoreactivation, excision repair and post reactive
recombination repair are generally error free repair
mechanism. However, there also exist an error prone and
mutation inducing repair called SOS repair.
• Error in both complementary strand of DNA would be
lethal for cell. Thus SOS repair reconstruct the chemical
structure of DNA but the heredity information is lost.
Hence SOS repair causes mutation along with repair of
DNA. DNA polymerase V help in SOS repair.
• It is also known as inducible repair. It involves more than
40 gene which encodes protein responsible for protection
and replication of DNA as well as repair and mutation.
• SOS response have been found in E. coli, Salmonella
Typhimurium, Mycobacterium tuberculosis etc, but not in
eukaryotic cell.
• It is not a single discrete mechanism but includes diverse
responses such as the ability to repair thymine dimers, to
induce various prophages, to shut off respiration, to delay
septum formation during cell division. These all responses
are regulated coordinately.
5.SOS REPAIR
(Fig1.0) SOS REPAIR MECHANISM

15. CONCLUSION:
Damage to DNA has the potential to cause cell death due to the
formation of dimers and mutations that disable the DNA from
replicating. This potential for cell death outlines the importance and
need for an efficient repair system that is able to either reverse the
effects or replace the damaged DNA.
Althrogh all mechanisms which helps in DNA Repair mechanisms has
more importence .

16. REFERENCES:
 MOLECULAR BIOLOGY Third edition.by phil turner alexander
McLennan, Andy Bates and Mike White .
 https://en.wikipedia.org/wiki/DNA_repair
 https://www.nobelprize.org/prizes/chemistry/2015/lindahl/f
acts/
 https://www.nobelprize.org/prizes/chemistry/2015/modrich
/facts/
 e May, N., Egly, J., & Coin, F. (2010). True lies: The double life
of the nucleotide excision repair factors in transcription and
DNA repair. Journal of Nucleic Acids, 2010, 1-10.
doi:10.4061/2010/616342
 Tanaka, M., Nakajima, S., Ihara, M., Matsunaga, T., Nikaido,
O., & Yamamoto, K. (2001). Effects of photoreactivation of
cyclobutane pyrimidine dimers and pyrimidine (6-4)
pyrimidone photoproducts on ultraviolet mutagenesis in
SOS-induced repair-deficient escherichia coli. Mutagenesis,
16(1), 1-6. doi:10.1093/mutage/16.1.1

17. THANK YOU.