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DNA REPAIR
Introduction
• DNA repair is a extremely crucial process for
the longetivity of an organism as during the
life of organisms DNA can be damaged by
variety of reasons and any such damage can
interfere with the functioning of cell and can
lead to death of cell.
DNA DAMAGE
• DNA damage caused by-
a. Deamination
b. Depurination
c. Radiations
d. Base analogs- 5-bromouracil
e. Intercalating agents- proflavin,
acridine,ethidium
•Cyotosine coverts into Uracil
•Adenine to hypoxanthine, base pair
with Cytosine
•Guanine to xanthine, base with
Cytosine but only by two H bonds
•Sometimes unnatural base are
coverted to natural bases such as the
conversion of 5-methyl cytosine to
Thymine
DEAMINATION: Spontaneous loss of
amino group
DEPURINATION: spontaneous hydrolysis of
the N-glycosyl linkage
Depurination results in abasic sugar
Alkylation and Oxidation
•Alkylation at the oxygen of carbon atom 6 of G : O6-metylguanine,
often mispairs with T.
•Oxidation of G generates oxoG, it can mispair with A and C. a G:C to
T:A transversion is one of the most common mutation in human
cancers.
DNA damage by UV
-Thymine dimer formation
•X-rays and gamma radiations cause double strand breaks
•Certain cancer drug such as bleomycin also cause breaks in
double strand
•Such agents are called clatogenic
Base analogs
Thymine analog
•By substitution of normal bases
•Structurally similar to normal base
Intercalating agents
•Are flat molecules containing several polycyclic rings that binds equally to the purine
or pyrimidine bases of DNA
•Cause the addition or deletion of base pairs
DNA REPAIR MECHANISMS
•Photoreactivation
•Methyl group removal
• Base excision repair
•Nucelotide excision repair
•Tranlesion DNA synthesis
•Transcription Coupled DNA repair
•Double strand break Repair
•Mismatch Repair
•SOS repair
•DNA repair is a collection of processes by which a cell identifies and corrects
damage to the DNA molecules that encode its genome
•The DNA repair ability of a cell is vital to the integrity of its genome and thus to
the normal functionality of that organism. Many genes that were initially shown to
influence life span have turned out to be involved in DNA damage repair and
protection
DIRECT REVERSAL OF DNA DAMAGE
PHOTOREACTIVATION
METHYL GROUP REMOVAL
BASE EXCISION REPAIR
-DNA glycosylase enzyme which are lesion specific
- 8 different type of glycosylases enzymes in a cell
oxoG:A REPAIR
-base flipping mechanism
- fail-safe glycosylase
NUCLEOTIDE EXCISION REPAIR
In E. coli UvrA, UvrB, UvrC and UvrD proteins, DNA plymerase and ligase
enzymes
MISMATCH REPAIR
SOS REPAIR
TRANSCRIPTION-COUPLED DNA REPAIR
-Involves recruitment to the
stalled RNA polymerase of
nucleotide excision repair
proteins
-It focuses repair on genes being
actively transcribed.
-TFIIH unwinds the DNA template
during the initiation of
transcription. Subunits of TFIIH
include the DNA helix-opening
proteins XPA and XPD.
TRANSLESION DNA SYNTHESIS
SUMMARY
THANK YOU

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DNA repair

  • 2. Introduction • DNA repair is a extremely crucial process for the longetivity of an organism as during the life of organisms DNA can be damaged by variety of reasons and any such damage can interfere with the functioning of cell and can lead to death of cell.
  • 3. DNA DAMAGE • DNA damage caused by- a. Deamination b. Depurination c. Radiations d. Base analogs- 5-bromouracil e. Intercalating agents- proflavin, acridine,ethidium
  • 4. •Cyotosine coverts into Uracil •Adenine to hypoxanthine, base pair with Cytosine •Guanine to xanthine, base with Cytosine but only by two H bonds •Sometimes unnatural base are coverted to natural bases such as the conversion of 5-methyl cytosine to Thymine DEAMINATION: Spontaneous loss of amino group
  • 5. DEPURINATION: spontaneous hydrolysis of the N-glycosyl linkage Depurination results in abasic sugar
  • 6. Alkylation and Oxidation •Alkylation at the oxygen of carbon atom 6 of G : O6-metylguanine, often mispairs with T. •Oxidation of G generates oxoG, it can mispair with A and C. a G:C to T:A transversion is one of the most common mutation in human cancers.
  • 7. DNA damage by UV -Thymine dimer formation •X-rays and gamma radiations cause double strand breaks •Certain cancer drug such as bleomycin also cause breaks in double strand •Such agents are called clatogenic
  • 8. Base analogs Thymine analog •By substitution of normal bases •Structurally similar to normal base
  • 9. Intercalating agents •Are flat molecules containing several polycyclic rings that binds equally to the purine or pyrimidine bases of DNA •Cause the addition or deletion of base pairs
  • 10. DNA REPAIR MECHANISMS •Photoreactivation •Methyl group removal • Base excision repair •Nucelotide excision repair •Tranlesion DNA synthesis •Transcription Coupled DNA repair •Double strand break Repair •Mismatch Repair •SOS repair •DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome •The DNA repair ability of a cell is vital to the integrity of its genome and thus to the normal functionality of that organism. Many genes that were initially shown to influence life span have turned out to be involved in DNA damage repair and protection
  • 11. DIRECT REVERSAL OF DNA DAMAGE PHOTOREACTIVATION METHYL GROUP REMOVAL
  • 12. BASE EXCISION REPAIR -DNA glycosylase enzyme which are lesion specific - 8 different type of glycosylases enzymes in a cell
  • 13. oxoG:A REPAIR -base flipping mechanism - fail-safe glycosylase
  • 14. NUCLEOTIDE EXCISION REPAIR In E. coli UvrA, UvrB, UvrC and UvrD proteins, DNA plymerase and ligase enzymes
  • 17. TRANSCRIPTION-COUPLED DNA REPAIR -Involves recruitment to the stalled RNA polymerase of nucleotide excision repair proteins -It focuses repair on genes being actively transcribed. -TFIIH unwinds the DNA template during the initiation of transcription. Subunits of TFIIH include the DNA helix-opening proteins XPA and XPD.