2. -:What is DNA repair-
⮚ DNA repair is a collection of processes by which a cell
identifies and corrects damage to the DNA molecules that
encode in genome.
⮚ Without the repair system, a genome would not be able to
maintain its essential cellular functions.
⮚ DNA carries all the necessary information for the growth and
function of the cell, and it is therefore important that any
inadvertent changes is not set right before it can become
detrimental to the cell.
⮚ The DNA repair machinery continuously scans the genome
and maintains genome integrity by removing any detected
damage.
⮚ DNA damage if not repaired may affect replication and
transcription, leading to mutation or cell death.
3. -:Why DNA needs to be repaired:-
➢ The repair of damage to both DNA strands is particularly
important in maintaining genomic integrity.
➢ The DNA damages can cause error during DNA replication or
inaccurate repair, leading to mutations that causes cancer.
➢ Damaged DNA if not properly repaired can lead to genomic
instability, apoptosis,that can greatly affect the organism’s
development.
4. -:Types of DNA repair:-
A variety of repair mechanism have evolved depending on type of
damage on DNA double helical structure.
1.Direct repair
a)uv radiation mediated damage
b) repair of damage caused by alkylating agents
2 . NER(nucleotide excision repair)
3. BER(base excision repair)
4. SOS repair
5. Direct repair
⮚ Applied to two main type of damage that is:
i)uv radiation mediated damage
ii)damage caused by alkylating agents
⮚ Acts directly on damage nucleotide, converting back to its
original structure.
⮚ Only a few types of nucleotides can be repaired directly.
6. i)Uv radiation mediated damage
⮚ Bacteria and several other organisms also possess another
mechanism to repair uv damage called photoreactivation.
⮚ This method is often referred to as “light repair” because it is
dependent on the presence of light energy.
⮚ Enzyme called DNA photolyase to split cyclobutane pyrimidine
dimers formed by uv light that block transcription.
7.
8. ii)repair of damage caused by alkylating agents
⮚ Methylation of guanine bases produces a change in DNA
structure by forming methylguanine that is complementary to
thymine rather cytosine so it pair with T not C during
replication.
⮚ DNA repair occurs by an enzyme (MGMT) methyl guanine
methyl transferase that transfer methyl group to its active site .
9. ◤
➢ABC exonuclease (composed of subunits
coded by uvrA,uvrB,uvrC genes) moves
along DNA and can detect Thymidine
dimers.
➢UvrA and UvrB complex attach on distortion
site then UvrA will dissociates.
➢UvrB attracts UvrC and nicks 5nucleotide at
3’ side of DNA while 8 nucleotides nicks at 5’
side of DNA will be produced by UvrC
subunit.
➢UvrD(DNA helicase ii) removes 12
oligonucleotides.
➢DNA polymerase I fills in gap in 5’-3’
directiom.
➢DNA ligase seals the gap.
NER
10. ◤
a) A DNA glycosylase recongnizes a
damaged base and cleaves between the
base and deoxyribose in the backbone.
b) An AP endonuclease cleaves the
phosphodiester backbone near the AP
site.
c) DNA polymerase I initiates repair
synthesis from the free 3’ OH at the
strand( with its 5’-3’ exonuclease activity)
and replacing it with undamaged DNA.
d) Then gap is sealed by DNA ligase.
BER(base excision
repair
11. SOS response
➢The SOS response is a coordinated cellular response and
aids in the survival of the organism by affecting the
expression of proteins that involved in cell division,
replication, recombation and excision repair.
➢The SOS response genes are induced when the bacterial
chromosome is extensively damaged.
➢The key regulatory elements are a repressor, called the
LexA repressor, and the RecA protein.
12. Mechanism
➢ In case of excessive DNA damage, stress condition
etc a cell responds by activating signal or RecA
protein.
➢ A RecA protein specifically binds to ss DNA to form a
nucleoprotein filament.
➢ The interaction of RecA with DNA activates RecA, which
then stimulates LexA to inactivate itself by self cleavage.
➢ With LexA inactivate, the level of expression of the SOS
genes increases & the error prone repair system is
activated.
➢ After DNA repair, the RecA protein loses its efficiency to
cause proteolysis and the LexA protein again bind to sos
operator & switch off the sos system.
13.
14.
15.
16. Diseases associated with defective DNA
repair system
● Ataxia telangiectasia
● Bloom syndrome
● Cockayne’s syndrome
● progeria
● xeroderma pigmentosum
● Hereditary non polyposis colon cancer
