核苷酸切除修复

Nucleotide excision repair (NER) is a DNA repair mechanism that removes and replaces damaged nucleotides caused by UV radiation and chemical mutagens. This process is critical for maintaining genome stability and preventing mutations that could lead to cancer or cell death. NER protects cells from environmental DNA damage by recognizing distortions in the DNA helix and excising the damaged region.

Repair proteins detect DNA damage through recognition of helix distortions caused by lesions. These proteins scan the DNA and identify abnormal structural changes rather than specific chemical modifications. Once damage is recognized, the repair machinery is recruited to the site to begin the excision and replacement process.

During excision, repair enzymes make cuts on both sides of the damaged DNA lesion, removing a segment containing the injury. The excised oligonucleotide is then replaced with newly synthesized DNA using the undamaged complementary strand as a template. This restoration process restores the original DNA sequence and function.

Nucleotide excision repair primarily targets bulky DNA lesions that distort the DNA helix, including UV-induced thymine dimers and adducts from chemical mutagens. These lesions create structural abnormalities that trigger NER recognition. The mechanism is particularly effective against environmental and chemical DNA damage.

Unlike base excision repair, which targets small lesions, nucleotide excision repair removes larger damaged segments and is triggered by helix distortion rather than specific base modifications. NER is also distinct from homologous recombination and strand invasion mechanisms, which address different types of DNA damage like double-strand breaks.

By removing and replacing damaged nucleotides before DNA replication, nucleotide excision repair prevents error-prone polymerases from incorporating incorrect bases opposite lesions. This proactive removal of damage maintains genetic fidelity and reduces mutation rates. Defects in NER genes are associated with increased cancer susceptibility.

UV radiation creates thymine dimers and other photoproducts that distort the DNA helix structure. These structural abnormalities are recognized by NER surveillance proteins, which initiate the repair cascade. The helix distortion serves as the primary signal for recruiting repair machinery to damaged sites.