site specific recombination
is illegitimate..
Transposase enzyme
recognized the self DNA
and cut it and also
recognized the target site.
Target site is not specific .

Transposons

 Reterovirus Like elements (RLE)- like reterovirus
 42 % human genome made up on
reterotransposons ..

Repair system
Direct Repair
1) Photoreactivation
Excision Repair
BER
NER
Mismatch
Transcriptional coupled
repair system
Double stranded
Break Repair
1.Homologous
recombination
2. Non-homologous
End joining Mech:
Single stranded DNA Repair
(Translession DNA Synthesis)
SOS
heavy damage 
translesion
polymerases
Any type of damage remove before cell division
Genetic information can be stored stably in DNA sequences only because a large set of DNA repair
enzymes continuously scan the DNA and replace any damaged nucleotides.

• Translession DNA Synthesis
• oxidizing agents , metabolites , radiation and reactive
chemicals DNA suffers heavy damage  translesion
polymerases
• When DNA damage is excessive, a special class of inaccurate
DNA polymerases, called translesion polymerases, is used to
bypass the damage, allowing the cell to survive but
sometimes creating permanent mutations at the sites of
damage.
• Y- Family DNA polymerase
• Lack of proofreading Activity
• Add nucleotide at lesion without base pairing
DNA Polymerase IV ---Din B Gene
DNA Polymerase V – UMU, UMUD Gene /------ Repressor Lex -A
SOS Repair / Translession DNA Synthesis /
Error prone Repair

DNA Polymerase IV ---Din B Gene
DNA Polymerase V – UMU, UMUD Gene /------ Repressor
Lex –A
In normal condition Lex –A Repressor protein bind to
Din B , UMU, UMUD Gene . And inhibit expression of
translesion polymerases.
Excessive DNA Damage or single strand DNA
Damage = High
Rec-A Protein Active and Interact with Lex-A and
Auto-Protease Activity of Lex-A is on.
Cleaved Lex-A – not bind to Din B , UMU, UMUD Gene
DNA Pol- IV DNA Pol-V
Absent Proofreading Activity
Add nucleotide at lesion without
base pairing

Double strand break repair
• Prokaryotic and lower eukaryotic – Homologous Recombination
• Higher eukaryotic – Non – Homologous End Joining (NHEJ)
Error prone Repair mechanism .

HOMOLOGOUS RECOMBINATION
• the mechanisms that allow the DNA sequences in cells to be
maintained from generation to generation with very little change.
• repair mechanism is essential for every proliferating cell
• homologous recombination (also known as general recombination)is an
exchange of DNA strands between a pair of homologous duplex DNA
• Work in meiosis in plants and animals.
• daughter DNA molecules are still held close together. homologous
recombination  flexible series of reactions

Prokaryotics
RecA first binds cooperatively to the invading single
strand, help to pairing of homologous strands.
Rec B,C,D – processing of ds DNA break.
5’3’ exonuclease
3’5’ Exonuclease
strand exchange protein complex
DNA Pol III and DNA Ligase
DNA synthesis and ligation
RUV-A,B – Branch Migration steps (Helicase Activity)
RUV-C – Resolution ( Holiday Junction)
 Both strand separate.

Homologous recombination in eukaryotic
• DNA Damage / Mutant sensor Kinase – ATM (Ataxia-Telangiectasia
Mutated kinase) .
• Sensory Kinase- chk-2 .
• Pairing of Homologous strands – BRCA-1, BRCA-2, WRN, Rad-5 .
• Processing of double strand Break – Rad-50,Rad 58,Rad 60 or MRX
complex in Yeast.
• Strand exchange protein Assembly – Rad 52, Rad 58.
• Resolution ( Holiday Junction)
 Both strand separate  Nuclease or resolvase

NHEJ
If these lesions were left unrepaired , they would
quickly lead to the breakdown of chromosomes
into smaller fragments and to loss of genes .
Nonhomologous end joining  loss of nucleotides
at the site of joining .
end-joining mechanism “quick and dirty” solution to
the repair of double-strand breaks  common in
mammalian somatic cells .
Age of 70.
Nonhomologous end joining  one broken
chromosome becomes covalently attached to
another. This can result in chromosomes with two
centromeres and chromosomes lacking
centromeres.

NHEJ
1. Recognition  Ku protein 70/80 
heterodimer binds to broken chromosome
ends.
2. End processing-> Additional proteins
(ARTEMIS,MRN) needed to hold the broken
ends together while they are processed and
eventually joined covalently.
3. Strand invasion , DNA synthesis and
Resolution
4. Ligation- Lig-IV