4. DNA EXCISION REPAIR
• By cut and patch mechanism
• Removes bulky lesions (pyrimidine dimers)
5. BASE EXCISION REPAIR IN ESCHERCHIA
COLI
By DNA glycosylases.
Recognition of the lesion in DNA
Removes the base outside the helix and detaching it
Creates AP site
AP endonucleases produces single nucleotide gap
Gap is filled by DNA polymerase I
DNA ligase joints the backbone
7. BASE EXCISION REPAIR IN HUMANS
Recognition of the lesion in DNA
the oxo G repair enzyme hOGG1 first binds non specifically to DNA
the oxoG is extruded from the double helix into a “G specific pocket”
the oxoG is inserted deeply into a lesion recognition pocket (oxoGpocket) on the
enzyme.
8. SHORT PATCH REPAIR
-the enzymes involved -glycosylase-associated β-lyase (apurinic/apyrimidinic endonuclease)
DNA polymerase β replaces the missing nucleotide, and the
DNA ligase 3–XRCC1 complex seals the gaps in the sugar–phosphate backbone
XRCC -“X-ray repair cross complementing rodent
repair deficiency
9. LONG PATCH REPAIR
APE1 makes an incision 5′ to the abasic site
2–10 nt are excised by FEN-1.
DNA polymerase δ or ε for long patch repairs
DNA ligase 1 for long patch repairs.
FEN1 flap
endonuclease 1
10.
11. NUCLEOTIDE EXCISION REPAIR IN ESCHERCHIA COLI
By multienzyme complex – ABC exinuclease
Uvr A Uvr B Uvr C
3 subunits
12. 2 Uvr A and Uvr B attaches to the damaged site
Uvr A leaves DNA & allows Uvr C (Uvr BC complex)
Uvr BC cuts the polynucleotide results in 12 nucleotide excision
excised DNA is removed & Uvr C leaves
Uvr B remains and prevents the pairing of single strand DNA
gap is filled by polymerase I and backbone is joined by Ligase.
Mechanism of Nucleotide excision repair
13.
14. NUCLEOTIDE EXCISION REPAIR IN HUMANS
Removes bulges from thymine–thymine dimers induced by UV irradiation
Six repair factors
RPA
XPA
XPC
TFII
H
XPG
XPF/ERCC1
15. MECHANISM
DNA is recognised by RPA, XPA, XPC, and the TFIIH complex
XPB and XPD unwinds the DNA double helix
incision is made on the 3′ side of the damage, by an endonuclease (XPG)
Another incision is made by a second endonuclease (XPF-ERCC1) on the 5′ side of the
damage
DNA polymerase ε or DNA polymerase δ, PCNA, RFC, and RPA for repair synthesis
gap in the DNA backbone is closed by DNA ligase I.
TFIIH-XPB
&XPD
RFC- Replication
factor C
Replication
protein A
PCNA-
Proliferating cell
nuclear antigen
16.
17. TYPES OF NUCLEOTIDE REPAIR
Transcription coupled pathway Global genomic pathway
18. XERODERMA PIGMENTOSUM
A child with xeroderma pigmentosum. Note
the abnormal dark pigmentation in parts of the body exposed
to sunlight
19.
20. REFERENCE
• Ajoy paul.,Textbook of cellular and molecular biology., 4th edition.,books and allied
publishers.,2015.,pg 1077-1087.
• Lizabeth A. Allison., Fundamental Molecular Biology., blackwell publishing.,2007.,
Australia.,pg 152-169.
