nucleotide excision repair
Summary
Nucleotide excision repair removes bulky, helix-distorting DNA damage, such as UV-induced thymine dimers, by cutting out a short stretch of the damaged strand. DNA polymerase refills the gap using the intact strand as template, and ligase seals it.
Detail
Meaning: Nucleotide excision repair (NER) removes bulky lesions that distort the double helix, such as thymine dimers made by UV light. The steps are: a protein complex recognizes the distortion; endonucleases cut the damaged strand on both sides of the lesion; a short single-stranded segment containing the damage is removed; DNA polymerase fills the gap in the 5′→3′ direction, using the intact complementary strand as template; DNA ligase seals the remaining nick. Because the undamaged strand supplies the template, the original sequence is restored.
On the MCAT: A passage describes UV exposure, or cells with defective repair genes as in xeroderma pigmentosum, and asks which pathway or step is missing. Expect to predict that cells lacking NER accumulate thymine dimers, which block replication and transcription and raise the mutation rate and cancer risk, especially in sun-exposed skin.
Common confusion: Students mix NER up with base excision repair and mismatch repair. Base excision repair uses a glycosylase to remove a single damaged base (such as uracil from cytosine deamination) and does not depend on a helix distortion. Mismatch repair fixes replication errors by recognizing the newly synthesized strand. NER cuts out a short stretch of nucleotides, not a single one.
Sources
- Lehninger Principles of Biochemistry
- Molecular Biology of the Cell
- Biochemistry (Berg, Tymoczko, Stryer)
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.