Best studied example of nucleotide excision repair is the repair of DNA damage

Best studied example of nucleotide excision repair is

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Best studied example of nucleotide excision repair is the repair of DNA damage caused by UV radiation. UV radiation can cause two thymines (Ts) that are adjacent to one another to fuse together to form a thymine dimer. This type of damage can only be removed by cutting away several nucleotides on each side of the lesion, so the damage is removed as a large oligonucleotide. Nucleotide Excision Repair:
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A. The damaged site, a thymine dimer in this case (blue rectangle), is recognized by the repair enzymes. B. and C. Repair enzymes remove a section of DNA that contains the damaged nucleotide. D. The gap is filled by a DNA polymerase. E. The remaining nick is sealed by a DNA ligase (ligase = to tie or join). Xeroderma pigmentosum (XP): Was the first disease demonstrated to be caused by defective DNA repair. Patients are photosensitive and highly susceptible to skin cancers in sun-exposed areas of the body; rates of skin cancer are 2000-5000 times higher than for the average person. Rare disease that can be caused by defects in any of the genes of the NER pathway. The left image shows the formation of thymine dimers as a result of UV damage. When the NER is functional, it repairs these dimers and the cells are fine. However, the defective NER pathway in XP means that UV damage, especially thymine dimers, cannot be effectively repaired and the damage accumulates in the DNA. While normal individuals can still experience DNA damage from UV radiation that results in skin cancer, those with a damaged repair pathway cannot repair that damage efficiently and will accumulate more mutations at a faster rate. This increased rate of mutation accumulation results in a higher probability of developing skin cancer. Homologous Recombination: Certain types of irradiation, such as exposure to x-rays or radioactivity, can completely severe the strands of a DNA double helix, leading to a double-strand break. These breaks, and other types of severe damage, can be re-joined through homologous recombination. When recombination takes place as a repair mechanism, the machinery locates the DNA sequence that has homology (nearly identical sequence) to both sides of the lesion and then uses the sequence of the intact DNA strands to fix the double-strand break. The process results in some of the sequence from the broken strand being incorporated into the intact strand, and vice versa. The DNA from both strands essentially becomes mixed, but if the sequences were highly homologous (basically identical), then the gene sequences are not affected.
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A. The double-strand break pieces (orange) are aligned with homologous regions (outlined in green) of undamaged DNA (blue) - usually from the second copy of the same chromosome. B. The strands of the undamaged DNA are used by several enzymes to help provide the needed sequence for the damaged DNA. C. As a result of the repair process, some of the sequence from each set of DNA strands has been "mixed".
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  • Winter '19
  • DNA, DNA Damage

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