Nucleotide excision repair

Definition

Nucleotide excision repair (NER) is a DNA repair mechanism that removes bulky DNA lesions and helix-distorting damage, such as those caused by UV radiation or chemical exposure. This process involves the recognition of damaged DNA, excision of the lesion, and synthesis of new DNA to fill the gap, thereby restoring the integrity of the genetic material.

5 Must Know Facts For Your Next Test

1. Nucleotide excision repair is crucial for correcting damage caused by UV light, which can create pyrimidine dimers that distort the DNA helix.
2. The NER process involves several key steps: damage recognition, unwinding of the DNA, excision of the damaged strand, and resynthesis using a DNA polymerase.
3. In humans, NER is primarily facilitated by a group of proteins known as the NER complex, which includes factors like XPA through XPG that coordinate the repair process.
4. Failure in nucleotide excision repair mechanisms can lead to serious consequences like increased mutation rates and a higher likelihood of developing cancers, particularly skin cancers.
5. NER can be categorized into two sub-pathways: global genome NER, which repairs damage throughout the genome, and transcription-coupled NER, which specifically repairs lesions that block active transcription.

Review Questions

• How does nucleotide excision repair identify and remove DNA damage?
  • Nucleotide excision repair identifies damaged DNA through specific recognition proteins that bind to distortions in the DNA helix. Once damage is detected, the DNA unwinds around the lesion, allowing an endonuclease enzyme to excise a short segment of the strand containing the damage. This process ensures that bulky lesions are removed effectively, enabling proper restoration of the genetic material.
• Discuss the role of proteins involved in nucleotide excision repair and their significance in maintaining genomic stability.
  • Proteins involved in nucleotide excision repair, such as XPA through XPG, play critical roles in recognizing damaged sites, unwinding the DNA, and coordinating the excision process. Their significance lies in maintaining genomic stability; any malfunction or deficiency in these proteins can lead to inefficient repair processes. This inefficiency can result in accumulated mutations, increasing the risk for diseases such as cancer.
• Evaluate the implications of defective nucleotide excision repair mechanisms on human health, particularly regarding skin cancer risk.
  • Defective nucleotide excision repair mechanisms have profound implications for human health, particularly as seen in disorders like xeroderma pigmentosum. Individuals with such defects exhibit heightened sensitivity to UV light due to their inability to effectively repair UV-induced DNA damage. This leads to an accumulation of mutations over time, significantly increasing their risk for skin cancers and other associated complications, highlighting the critical role of NER in safeguarding cellular integrity and preventing tumorigenesis.

Related terms

DNA polymerase: An enzyme that synthesizes new DNA strands by adding nucleotides complementary to the template strand during DNA replication and repair.

xeroderma pigmentosum: A rare genetic disorder characterized by extreme sensitivity to UV radiation due to defects in nucleotide excision repair, leading to a higher risk of skin cancer.

base excision repair: A DNA repair pathway that removes and replaces damaged bases in DNA, distinct from nucleotide excision repair which targets larger lesions.