Base excision repair (BER) and nucleotide excision repair (NER) are two major DNA excision repair systems. They follow a complex repair pathway in eukaryotes whereas a prototype system exists in prokaryotes. The two pathways of BER and NER have four steps: (1) recognition of damaged DNA, (2) excision of damaged DNA, (3) DNA synthesis to fill the nucleotide gap, and (4) sealing of nicks in the DNA.
Base Excision Repair
Base excision repair (BER) is a repair pathway that repairs the replicating DNA throughout the cell cycle. It ensures that mutations are not incorporated into the newly replicating DNA strands. Adenine, cytosine, guanine and thymine are prone to alkylation (addition of an alkyl group), deamination (removal of an amine group) and oxidation (damage by reactive oxygen species). These activities can cause substitution or deletion in the base pairs of DNA that can lead to perpetuation of mutation.
The process of base excision repair begins by identification and removal of the mutated base by the DNA glycosylase enzyme. It catalyses the N-glycosidic bond between the sugar and a base. This creates an apurinic/apyrimidinic (AP) site. Next, another enzyme called AP endonuclease nicks the abasic site, creating a break in the strand of DNA. In the next two steps, DNA polymerase fills in the gap created by endonuclease and DNA ligase seals it.
Nucleotide Excision Repair
Nucleotide excision repair (NER) is a damage repair pathway that exists in all organisms. It repairs damages made by UV light, chemicals adducts, radiations and other mutagens. The resulting damages can cause distortion to the DNA helix.
The pathway of nucleotide excision repair is complex, but can be simplified as: removal of damaged stretch of DNA, resynthesis of the removed fragment by taking undamaged fragments as template and finally ligation of the fragments.
Xeroderma pigmentosum is a genetic disease caused by a defect in the XPC enzyme. The enzyme XPC removes UV lesions caused by daily exposure of UV rays from the sun.
BER vs NER
|Base Excision Repair||Nucleotide Excision Repair|
|Base excision repair is a pathway that repairs replicating DNA throughout the cell cycle.||Nucleotide excision repair is a pathway that repairs constantly damaging DNA due to UV rays, radiation and mutagens.|
|Removal of Damaged DNA|
|A single base is removed which creates an abasic site in the DNA strand.||A short, single-stranded stretch of the affected DNA strand is removed.|
|Cause of DNA Damage|
|It repairs DNA that is damaged by endogenous mutagens.||It repairs DNA that is damaged by exogenous mutagens.|
|Initial Cleavage Site|
|The initial cleavage is directed at the glycosidic bond that joins the purine or pyrimidine base to the deoxyribose sugar of the DNA.||In NER, the initial cleavage is directed towards the phosphodiester bond that connects the 3’ end of one sugar to the 5’ end of another sugar.|
|Nature of Repair|
|It repairs small damages that do not distort the helix lesion of a genome.||It repairs bulky helix-distorting lesions in a genome.|
|First Enzyme that Recognises the Damaged Site|
|DNA Glycosylase||XPC in eukaryotes and UvrABC in prokaryotes|
|What Type of Modifications Does It Repair?|
|It repairs bases that are prone to alkylation, deamination and oxidation.||The NER pathway can repair a wide spectrum of damaged DNA. It can remove structurally unrelated base modifications such as those caused by UV light (pyrimidine dimers), benzopyrenes, aflatoxins and other chemotherapeutic agents.|
|Defects in this pathway can lead to cancer.||Defects in this pathway cause xeroderma pigmentosum, Cockayne syndrome and also cancer predispositions.|
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