DNA repair is the process by which cells use enzymes to repair mutations in DNA and restore it to its original state. The most common types of DNA damage are single-strand breaks and base damages, which occur at a rate of around 10,000 per cell daily. Single-strand repair uses the undamaged complementary strand as a template. Direct reversal repair directly removes damaged bases using specialized proteins. Double-strand breaks are more dangerous and can be repaired by homologous recombination or non-homologous end joining, with the latter sometimes resulting in lost nucleotide information.

1. Presented by
Mr.Karthick J.

2. DNA repair
The process by which a cell uses a series of special enzymas to
repair mutations (changes) in DNA and restore the DNA to its
original state. The DNA is constantly mutating and being repaired.
This repair process is controlled by special genes.

3.  Single-strand base damages and single-strand breaks are the
most common types of DNA damage.
 The daily rate of single-strand breaks caused by reactive oxygen
and nitrogen are estimated to occur at a frequent rate of 10000
per cell per day

5.  As only one strand suffers a defect, the other complementary
strand in the double helix could be used as a template
reference to correct the damages.
 In a Watson-Crick DNA base pairing, adenine (A) forms a
base pair with thymine (T) and guanine (G) forms a base pair
with cytosine ©. Our body uses this base pairing information
to identify incorrect base pairings and also, the correct
nucleotide needed to replace the damaged base.

6.  Types of single-strand repair mechanisms used in our body:

 Direct Reversal
 Base Excision Repair
 Nucleotide Excision Repair
 Mis-match Repair

7. • Most cases of DNA damage are not reversible. For
cases that are reversible, our body uses direct reversal
repair mechanism to correct the damaged base.
• Direct reversal repair is a mechanism of repair where
the damaged area or lesion is repaired directly by
specialised proteins in our body.
• It is the simplest form of DNA repair and also, the
most energy efficient method.
• It does not require a reference template unlike the
other single-strand repair mechanism. Moreover, it
does not involve the process of breaking the
phosphodiester backbone of the DNA

9.  An example of reversible DNA damage repairable via Direct
Repair is Alkylation which can be repaired via direct removal
of the Alkyl groups.
 Alkylating agents are carcinogens that is capable of alkylating
DNA in our body. It is widely used to create medicines (e.g.,
treatment of leukaemia, tumors ) and industrial chemicals.
 Alkylated DNA bases resulted in improper base pairing and
ultimately, lead to cell death.
 An example of Alkylation is Methylation which is the
addition of a methyl group (CH3) to a guanine (G) nucleotide.
This resulted in a complementary pairing to thymine (T)
instead of cytosine ©.

11.  Direct reversal repair involves using a sacrificial protein for
the removal of each Alkyl group since each protein is
permanently inactivated upon transfer of alkyl group to
protein. An example of enzyme involved in direct reversal
repair is Methyltransferase.
 MGMT is a critical enzyme used in the direct reversal of DNA
damage, O6-alkylguanine in our body. It is a common protein
found in all types of living organisms ranging from
prokaryotes to eukaryotes .

12. Direct repair of Nick’s
A Nick is a discontinuity in a double standard DNA
molecule where there is no phosphodiester damage or enzyme
action. DNA ligases are versatile and ubiquitous enzyme that
catalyzes the formation of phosphodiester bond between 3’
hydroxyl at the end of one DNA strand and 5’ phosphate at the
end of another strand, making them essential in nicked DNA
repair.

13.  Double stand breakage occurs when two strands of the DNA is
being broken or damaged.
 This type of damage poses very disastrous effects if left
unrepaired.
 DNA double-strand breaks are highly potent inducers of
genotoxic effects (chromosomal breaks and exchanges) and cell
death

15.  There are 2 types of mechanism which repairs this type of
double strand DNA damage, namely homologous
recombination (HR) and non-homologous end joining (NHEJ)
 The latter is more dangerous as although it repairs the break,
some information of nucleotides are usually lost at repair site
and it is almost impossible to replicate back the original
nucleotide information.

16.  Whether homologous recombination or NHEJ is used to repair
double-strand breaks is largely determined by the phase of cell
cycle.
 NHEJ occurs mainly in G0/G1 and early S phase, whereas HR
occurs during the late S and G2 phases

18. Thank you