Difference Between Mismatch Repair and Nucleotide Excision Repair

The main difference between mismatch repair and nucleotide excision repair is that mismatch repair (MMR) is responsible for the removal of base mismatches and small insertion/deletion loops introduced during DNA replication, whereas nucleotide excision repair (NER) is responsible for the removal of a variety of DNA damages that occur due to ultraviolet radiation. Furthermore, cells undergo mismatch repair immediately after DNA synthesis while cells undergo nucleotide excision repair if DNA gets damaged. 

Mismatch repair and nucleotide excision repair are two mechanisms which prevent mutations and other permanent changes in the DNA sequence. 

Key Areas Covered 

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

Key Terms 

DNA Damage, DNA Repair, Mismatch Repair (MMR), Nucleotide Excision Repair (NER), Replication Errors

What is Mismatch Repair 

Mismatch repair (MMR) is a DNA repair mechanism that occurs just after DNA replication. Therefore, the main objective of this mechanism is to remove and replace mispaired bases, which are not fixed by proofreading. Moreover, it detects and corrects small insertions and deletions that occur due to the slips of the DNA polymerase. 

Figure 1: Mismatch Repair Mechanism

Usually, the three proteins in the E. coli mismatch repair system are MutS, MutL, and MutH. On the other hand, eukaryotes contain only the homologous of MutS and MutL. In humans, MutS-homologous heterodimer, MSH2- MSH6 binds to the mismatch while MSH2-MSH6 and MSH2-MSH3 can bind to the insertions/deletions loop. Then, the newly-synthesized strand is degraded, removing the mismatch by the action of EXO1. After that, resynthesis of DNA and ligation complete the mismatch. 

What is Nucleotide Excision Repair 

Nucleotide excision repair (NER) is a DNA repair mechanism to remove and replace damaged nucleotides. Generally, this mechanism detects and corrects DNA damages, which distort DNA double helix. That is; this pathway detects nucleotides and modifies with bulky chemical groups attached to DNA such as chemicals in cigarette smoke. Furthermore, the nucleotide excision repair pathway fixes DNA damages caused by UV radiation. Here, UV radiation makes thymine and cytosine bases to react with their adjacent nucleotides. However, the resultant bonds distort the double helix, causing errors in DNA replication. Here, the most common type of these bonds are the thymine dimers, consisting of two thymine nucleotides reacted together.

Figure 2: Nucleotide Excision Repair

Moreover, the two subpathways of nucleotide excision repair are global genome repair (GGR), which repair damages in the overall genome, and transcription-coupled repair (TCR), which specifically repair the transcribed strand of active genes. However, these two pathways use different factors for the initial recognition step. After that, the recruiting transcription factor, TFIIH has two domains with helicase activity of opposite polarity to unwind the DNA around the lesions. Then, the secondly binding transcription factors cut the damage from its 3′ and 5′ ends. From that, a 24-32 nucleotides-long fragment is released. Finally, the repair is completed by DNA synthesis and ligation. 

Similarities Between Mismatch Repair and Nucleotide Excision Repair 

• Mismatch repair and nucleotide excision repair are two types of DNA repair mechanisms. 
• The main function of them is to prevent mutations and other permanent changes in the DNA sequence. 
• Enzymes carry out both processes. 

Difference Between Mismatch Repair and Nucleotide Excision Repair 

Definition 

Mismatch repair (MMR) refers to a DNA repair system whereby one member of a mismatched pair of bases is converted to the normally matched base while nucleotide excision repair (NER) refers to the main pathway used by mammals to remove bulky DNA lesions such as those formed by UV light. 

Significance 

Cells undergo mismatch repair immediately after DNA synthesis while cells undergo nucleotide excision repair with the occurrence of DNA damages. 

Type of Repair 

Mismatch repair replaces mismatches and insertion/deletion loops, which are not repaired by proofreading while nucleotide excision repair replaces DNA damages formed by UV radiation or chemicals in the cigarette smoke. 

Excision by 

Exonuclease 1 excises mismatched DNA in the mismatch repair mechanism while the transcription factors, XPG and XPF-ERCC1 excise the damaged DNA in the nucleotide excision repair mechanism. 

Conclusion 

Mismatch repair is the mechanism of DNA repair, replacing the mismatches and insertion/deletion loops incorporated during DNA replication. Generally, these mismatches are the escaped ones during proofreading. On the other hand, nucleotide excision repair is another mechanism of DNA repair, which replace the damaged DNA by UV radiation. Therefore, mismatch repair occurs just after DNA replication. However, nucleotide excision repair mechanisms occur with the occurrence of DNA damages. The main function of both mechanisms is to prevent mutations and other permanent changes in DNA. Thus, the main difference between mismatch repair and nucleotide excision repair is the type of repair. 

 References:

1. Fleck, O. “DNA Repair.” Journal of Cell Science, vol. 117, no. 4, 2004, pp. 515–517., doi:10.1242/jcs.00952.

Image Courtesy:

1. “DNA mismatch repair Ecoli” By Kenji Fukui (CC BY 4.0) 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