What is the Difference Between Base Excision Repair and Nucleotide Excision Repair

The main difference between base excision repair and nucleotide excision repair is that the base excision repair pathway corrects only the damaged bases, which are non-bulky lesions, whereas the nucleotide excision repair pathway corrects bulky DNA adducts through the removal of a short-single stranded DNA segment along with the lesion. Furthermore, base excision repair mechanisms mainly process modifications occurring due to deamination, alkylation, and oxidation. But, the nucleotide excision repair mainly processes the DNA damages induced by UV light, including thymine dimers and  6,4-photoproducts.  

In brief, the base excision repair and nucleotide excision repair are two of the three types of excision repair pathways, which correct DNA damages. Generally, DNA damages can occur as a result of mutagens, chemical agents or radiation. Also, they contribute to numerous diseases and cancer. 

Key Areas Covered 

1. What is Base Excision Repair
     – Definition, Process, Importance
2. What is Nucleotide Excision Repair
     – Definition, Process, Importance
3. What are the Similarities Between Base Excision Repair and Nucleotide Excision Repair
     – Outline of Common Features
4. What is the Difference Between Base Excision Repair and Nucleotide Excision Repair
     – Comparison of Key Differences

Key Terms 

Base Excision Repair, DNA Adducts, DNA Damages, Excision Repair, Nucleotide Excision Repair

What is Base Excision Repair 

Base excision repair (BER) is one of the excision repair mechanisms, removing small, non-helix-distorting DNA damages caused by chemical agents or mutagens. Therefore, one of the main significant features of base excision repair is that it repairs small lesions. Here, this type of lesions affects the hydrogen bonding and base pairing of complementary bases in the DNA. Thereby, they may result in mutations by mispairing, or it may lead to breaks of the DNA during replication. Generally, the three mechanisms of chemical damages of DNA, resulting in single-base changes are alkylation, deamination, and oxidation.

Figure 1: Base Excision Repair

Furthermore, DNA glycosylases are the enzymes responsible for the initiation of base excision repair by recognizing DNA damages, forming an AP site by flipping the damaged base out of the double helix. Then, AP endonuclease cuts the AP site, leaving a 3′ OH adjacent to a 5′ deoxyribose phosphate (dRP). After that, the resulting single-strand break may proceed either as a short-patch, replacing a single nucleotide or as a long patch, replacing 2-10 nucleotides. Subsequently, the pol β is responsible for catalyzing short-patches while pol δ and pol ε are responsible for catalyzing long-patches. For instance, the flap endonuclease, FEN1 removes the 5′ flap generated in the long-patches. Finally, DNA ligase III seals the nick in short-patched, while the DNA ligase I seals the nick in long-patches. 

What is Nucleotide Excision Repair 

Nucleotide excision repair (NER) is another mechanism of excision repair responsible for the removal of bulky and helix-distorting DNA damages mainly caused by UV light. In comparison to BER, NER repairs bulky DNA adducts such as thymine dimers and 6,4-photoproducts. Furthermore, the main characteristic feature of the nucleotide excision repair is the removal of a short-fragment of single-stranded DNA in contrast to the few bases as in base excision repair. Ultimately, DNA polymerase resynthesizes the missing fragment according to the bases in the complementary strand.

Figure 2: Nucleotide Excision Repair

Moreover, there are two pathways of nucleotide excision repair. They are global genomic NER (GG-NER or GGR) and transcription-coupled NER (TC-NER or TCR). Here, the main difference between the two pathways is how they recognize DNA damages. However, both pathways proceed similarly in excision of the damage, repair, and ligation. Basically, in global genomic NER, DNA-damage binding (DDB) and XPC-Rad23B complexes are responsible for the recognition of DNA damages. On the other hand, in the transcription-coupled NER, the repair mechanism initiates when RNA polymerase stalls at a lesion in DNA. Subsequently, TFIIH is the enzyme responsible for the dual incision and XPG and XPF-ERCC1 excise the lesion. Finally, after the restoration of the original nucleotide sequence by pol δ, ε and/or κ, DNA ligase I and FEN1 or DNA ligase III seal the nick. 

Similarities Between Base Excision Repair and Nucleotide Excision Repair

• Base excision repair and nucleotide excision repair are two of the three excision repair mechanisms while the third being DNA mismatch repair (MMR). 
• Both mechanisms correct DNA damages caused by chemicals, radiation or mutagens. 
• Generally, DNA damages cause structural changes in DNA, preventing the replication mechanisms from functioning properly. 
• Therefore, DNA damages may contribute to numerous diseases and cancer. 
• Both excision repair mechanisms are single-stranded damage repair responsible for cutting the damaged DNA strand and resynthesizing according to the remaining complementary DNA strand. 
• Here, enzymes or protein complexes are responsible for the removal of damaged DNA while DNA polymerase resynthesizes the removed DNA. Finally, DNA ligase I and FEN1 in long-patches or DNA ligase III in short-patches seal the nick seals the nick. 

Difference Between Base Excision Repair and Nucleotide Excision Repair

Definition 

Base excision repair refers to a cellular mechanism, repairing damaged DNA by removing small, non-helix-distorting base lesions from the genome while nucleotide excision repair refers to a DNA repair mechanism particularly important in removing DNA damages induced by ultraviolet (UV) light. 

Type of DNA Damages 

Base excision repair corrects small, non-helix-distorting lesions while nucleotide excision repair corrects bulky, helix-distorting lesions. 

Type of DNA Damages – Examples 

Base excision repair mechanisms mainly process modifications occurring due to deamination, alkylation, and oxidation while nucleotide excision repair mainly processes DNA damages induced by UV light.  

Type of Changes 

Base excision repair corrects mainly chemical damages, which affect hydrogen bonding and regular base pairing while nucleotide excision repair corrects thymine dimers and  6,4-photoproducts. 

DNA Damages Caused by 

Base excision repair corrects damages caused by endogenous mutagens while nucleotide excision repair corrects the damages caused by exogenous mutagens. 

Excision of the DNA Damage 

DNA glycosylases and AP endonucleases are responsible for the recognition and removal of DNA damage in base excision repair while proteins including DDB and XPC-Rad23B are responsible for the recognition and XPG and XPF-ERCC1 are responsible for the excision of DNA damages in nucleotide excision repair. 

Removal of the DNA Damage 

In base excision repair, few bases are removed while in nucleotide excision repair, a short, single-stranded fragment is removed along with the DNA damage. 

Diseases 

Defected base excision repair mechanisms can contribute to the development of cancer while the defected nucleotide excision repair mechanisms can cause Xeroderma pigmentosum and Cockayne’s syndrome. 

Conclusion 

Base excision repair is a type of excision repair mechanism responsible for the removal of DNA damages caused by chemical agents and mutagens. Generally, this type of DNA damages is small and non-helix-distorting. Also, in order to remove them, the repair mechanism only removes the damaged bases. On the other hand, nucleotide excision repair is another type of excision repair mechanism responsible for the removal of DNA damages mainly caused by UV light. However, they are bulky lesions, which are helix-distorting. On the other hand, the nucleotide excision repair mechanism removes a short fragment of DNA along with the damage, which is resynthesized later by DNA polymerase. Therefore, the main difference between base excision repair and nucleotide excision repair is the type of DNA damages they repair and their mechanisms of DNA damage repair. 

References:

1. Memisoglu, A, and L Samson. “Contribution of base excision repair, nucleotide excision repair, and DNA recombination to alkylation resistance of the fission yeast Schizosaccharomyces pombe.” Journal of bacteriology vol. 182,8 (2000): 2104-12. doi:10.1128/jb.182.8.2104-2112.2000.

Image Courtesy:

1. “BER basic pathway” By Amazinglarry (talk) at en.wikipedia – Created by author (Public Domain) via Commons Wikimedia   
2. “Nucleotide Excision Repair-journal.pbio.0040203.g001” By Jill O. Fuss, Priscilla K. Cooper (CC BY 2.5) via Commons Wikimedia