Nucleotide Excision Repair and Base Excision Repair

Excision repair removes a damaged segment of one DNA strand and resynthesises it using the intact complementary strand as a template. Two pathways share this logic but handle different lesions: base excision repair corrects small, non-helix-distorting base damage, while nucleotide excision repair removes bulky, helix-distorting lesions such as those caused by ultraviolet light. Both restore the original sequence without leaving a permanent change.

Definition

Base excision repair (BER) removes single damaged or inappropriate bases through a DNA glycosylase and processes the resulting abasic site, whereas nucleotide excision repair (NER) recognises bulky, helix-distorting lesions and excises a short oligonucleotide containing the damage; both then fill and seal the gap by template-directed synthesis and ligation.

Scope

This entry contrasts the two excision-repair pathways: the substrates each recognises, the enzymes that carry out recognition, excision, gap filling, and ligation, and the distinction within nucleotide excision repair between global-genome and transcription-coupled subpathways. It is a mechanistic reference and does not address clinical management.

Core questions

• What kinds of lesion does each pathway recognise?
• How does base excision repair process an abasic site after the base is removed?
• How does nucleotide excision repair excise a damaged oligonucleotide?
• What is the difference between global-genome and transcription-coupled NER?

Key concepts

• DNA glycosylase
• Abasic (AP) site and AP endonuclease
• Short-patch and long-patch BER
• Helix-distorting bulky lesions
• Dual incision in NER
• Global-genome NER
• Transcription-coupled NER
• Gap filling and ligation

Mechanisms

Base excision repair begins when a DNA glycosylase recognises and removes a single damaged or inappropriate base, such as uracil or 8-oxoguanine, leaving an abasic site; an AP endonuclease then incises the backbone, a polymerase fills the gap, and a ligase seals it, with short-patch and long-patch variants differing in the number of nucleotides resynthesised. Krokan and Bjørås describe how this pathway is the principal route for the small, frequent base lesions that arise from oxidation, deamination, and alkylation. Nucleotide excision repair instead recognises the helical distortion produced by bulky adducts and ultraviolet photoproducts; a multiprotein complex verifies the lesion, makes incisions on either side, and removes a short oligonucleotide, after which the gap is filled and sealed. Schärer details the two NER subpathways: global-genome NER surveys the whole genome for distortions, while transcription-coupled NER is triggered when RNA polymerase stalls at a lesion in a transcribed strand.

Clinical relevance

Inherited defects in nucleotide excision repair cause xeroderma pigmentosum, with extreme sensitivity to ultraviolet light and a high skin-cancer risk, and related disorders such as Cockayne syndrome, illustrating the importance of these pathways; this entry presents those associations as mechanistic background rather than as guidance for diagnosis or care of any individual.

History

Excision repair was among the first repair processes to be defined biochemically, with the recognition in the 1960s that cells can excise ultraviolet-damaged segments and resynthesise them. Subsequent reconstitution of the human pathways established the enzymes involved, and the distinction between global-genome and transcription-coupled subpathways clarified why some repair-deficiency syndromes affect the whole genome while others chiefly affect transcribed genes.

Key figures

• Aziz Sancar
• Tomas Lindahl
• Orlando Schärer
• Hans Krokan

Seminal works

• sancar-2004
• scharer-2013
• krokan-bjoras-2013

Frequently asked questions

What is the main difference between base excision repair and nucleotide excision repair?

Base excision repair removes a single damaged base and the resulting abasic site for small, non-distorting lesions, while nucleotide excision repair removes a short stretch of nucleotides around a bulky, helix-distorting lesion such as a UV photoproduct.

What is transcription-coupled repair?

It is a branch of nucleotide excision repair that is triggered when RNA polymerase stalls at a lesion in a transcribed strand, allowing damage in active genes to be repaired preferentially.