NUCLEOSIDE EXCISION REPAIR
Nucleotide Excision Repair
(NER) is a DNA repair mechanism that addresses a wide range of DNA lesions,
including those induced by ultraviolet (UV) light, environmental chemicals, and
other bulky DNA lesions that distort the normal helical structure. NER is a
versatile and evolutionarily conserved process that operates in both
prokaryotes and eukaryotes. Let's explore the key steps involved in Nucleotide
Excision Repair:
1. Recognition of DNA Damage:
- Damage Sensing:
The process begins with the recognition of bulky lesions or distortions in
the DNA helix. Various proteins, including XPC-RAD23B in eukaryotes, are
involved in sensing and recognizing DNA damage.
- Verification:
The recognition is often followed by a verification step to ensure that
the detected distortions are indeed indicative of DNA damage.
2. Formation of a
Pre-incision Complex:
- Recruitment of Proteins:
Once damage recognition is confirmed, several proteins, including the
transcription factor TFIIH, are recruited to form a pre-incision complex
at the site of damage.
- Opening of the DNA Helix:
TFIIH helicase activity unwinds the DNA helix in the vicinity of the
lesion, creating a bubble structure that exposes the damaged region.
3. Dual Incision:
- Endonucleolytic Cleavage:
Two incisions are made on the damaged DNA strand, one on each side of the
lesion.
- Excision of the Damaged Oligonucleotide:
The segment of the damaged DNA strand containing the lesion is then
excised.
4. DNA Repair Synthesis:
- DNA Polymerase Action:
DNA polymerase is recruited to the site, synthesizing a new DNA strand
complementary to the undamaged strand.
- Ligation:
The newly synthesized DNA strand is then ligated to the existing DNA,
sealing the gap.
5. Final Verification and
Restoration:
- Proofreading and Surveillance:
DNA polymerases involved in NER have proofreading capabilities,
contributing to the accuracy of the repair. Surveillance mechanisms also
monitor the repaired DNA for any potential errors.
Key Features and
Significance:
- Versatility:
Nucleotide Excision Repair is versatile, addressing a broad spectrum of
bulky DNA lesions, including those induced by UV radiation and
environmental carcinogens.
- Global Genome Repair (GGR) and
Transcription-Coupled Repair (TCR): In eukaryotes, there
are two subpathways of NER: GGR, which operates throughout the genome, and
TCR, which prioritizes repair of lesions in actively transcribed genes.
- Maintenance of Genomic Integrity:
By recognizing and repairing bulky lesions that can lead to mutations or
disruptions in DNA structure, NER plays a crucial role in maintaining
genomic integrity.
- Association with Human Diseases:
Defects in NER are associated with several human disorders, including
xeroderma pigmentosum (XP), which is characterized by extreme sensitivity
to UV light and a high risk of skin cancer.
Nucleotide Excision Repair is
a vital cellular process that contributes to the prevention of mutations and
the preservation of genomic stability. Its ability to address a wide range of
DNA lesions underscores its importance in cellular homeostasis and the
protection against the deleterious effects of DNA damage.
Mind Map Table: Nucleotide Excision Repair (NER)
| Step | Enzyme/Protein | Key Feature | Significance |
|---|---|---|---|
| Recognition of DNA Damage | XPC-RAD23B (eukaryotes), other proteins | Damage sensing and verification | Versatility in addressing a wide range of DNA lesions |
| Formation of a Pre-incision Complex | TFIIH and other recruited proteins | Opening of the DNA helix, creating a bubble structure | Recognition and recruitment of proteins to the damaged site |
| Dual Incision | Endonucleolytic cleavage | Excision of the damaged oligonucleotide | Removal of the lesion from the DNA strand |
| DNA Repair Synthesis | DNA polymerase | Synthesis of a new DNA strand, complementary to the undamaged | Restoration of the DNA sequence after lesion excision |
| Final Verification and Restoration | DNA polymerases with proofreading capabilities | Proofreading and surveillance mechanisms | Maintenance of genomic integrity and prevention of mutations |
| Surveillance mechanisms | |||
| Key Features and Significance | Versatility in repairing a broad spectrum of DNA lesions | Global Genome Repair (GGR) and Transcription-Coupled Repair (TCR) | Vital role in maintaining genomic stability, preventing mutations |
| Association with human diseases (e.g., xeroderma pigmentosum) | Maintenance of genomic integrity | Defects in NER associated with disorders, highlighting its importance |