1.
DNA REPAIR
D.INDRAJA

2.
REPAIR --- ? (when should be done)
DAMAGEREPAIR
RATE OF DNA DAMAGE = RATE OF DNA REPAIR
Healthy cell
RATE OF DNA DAMAGE > RATE OF DNA REPAIR
Diseased cell

3.
Why only DNA but not
RNA,Protein,lipid etc
All these others can be replaced but
DNA must be preserved

4.


5.
DNA Damage

6.
C U
A  H
MC T
G X

7.
• What does DNA have to do with cancer? Cancer occurs when
cells divide in an uncontrolled way, ignoring normal "stop"
signals and producing a tumor. This bad behavior is caused by
accumulated mutations, or permanent sequence changes in the
cells' DNA.
• Replication errors and DNA damage are actually happening in
the cells of our bodies all the time. In most cases, however, they
don’t cause cancer, or even mutations. That’s because they are
usually detected and fixed by DNA proofreading and repair
mechanisms. Or, if the damage cannot be fixed, the cell will
undergo programmed cell death (apoptosis) to avoid passing on
the faulty DNA.
• Mutations happen, and get passed on to daughter cells, only
when these mechanisms fail. Cancer, in turn, develops only
when multiple mutations in division-related genes accumulate in
the same cell.

8.
Mechanisms used by cells to correct replication errors and fix DNA damage
• Proofreading
DNA polymerases are the enzymes that build DNA in cells. During DNA replication
(copying), most DNA polymerases can “check their work” with each base that they
add. This process is called proofreading. If the polymerase detects that a wrong
(incorrectly paired) nucleotide has been added, it will remove and replace the
nucleotide right away, before continuing with DNA synthesis.

9.
DNA Repair
DNA repair is a collection of processes by which a cell identifies and
corrects damage to the DNA molecules that encode its genome
•It takes place before the cell divison takes place that is G2 phase of cell
cycle

10.
Mechanism of mismatch repair

11.
Mismatch repair -Based on which end

12.
E.coli Humans and other eukaryotes

13.
Sos response
when there is UV damage in DNA then the replication fork stalling
occurs it is recovered by the process of photoreactivation by the
enzyme photolyases then repairs uv damaged DNA
DNA damage by U.V
Replication fork stalling
Photo reactivation
photolyases
Repairs UV damaged DNA

14.
• When the DNA damage is extensive there is no use of photolyases
then the replication fork stalling is by-passed by sos response
which first involves NER(nucleotide excision repair) and when the
damage is not cured then DNA translesion synthesis (pol V) occurs
(sos repair) which bypass the RNA polymerase with out curing so
it is called as error prone repair
Extensive DNA damage
Replication fork stalling photolyases
By pass
Sos response
NER
DNA translesion synthesis
(fails)

15.
• During normal growth the sos genes are negatively regulated by
lexA repressor protein dimers.under normal conditions lexA binds to
20bp consenses sequence the sos box in the promoter region for
those genes
• Activation of sos genes occurs after DNA damage by the
accumulation of ss DNA regions generated at replication forks
where DNA polymerase is blocked .

16.
Rec A forms a filament around these ss DNA regions in ATP
dependent fashion and become activated .the activated form of Rec A
interacts with the lex A repressor to facilitate the lex A repressors self
clevage from the promoter

17.
• Operators that bind lex A weakly are the first to be fully expressed in
this way lex A can sequentially activate different mechanisms of repair
genes having a weak sos box thus the first sos repair mechanism to be
induced is NER whose aim to fix DNA damage with out commitment
to a full fledged sos response if NER do not fix the DNA damage then
pol V is synthesized
UVR-A gene UMU C gene UMU D gene
DNA polymerase V
(translesion synthesis)
UVR ABC
Endonuclease
NER
DNA damage
Rec A
Initiates autocatalysis
Clevage of lexA
RNA
POL
lexA

18.
Protein kinases