The main difference between base excision repair and mismatch repair is that base excision repair is mainly responsible for repairing small non-bulky lesions in DNA, such as damaged or incorrect bases and single-strand breaks, whereas mismatch repair is mainly responsible for correcting errors that occur during DNA replication, including mismatches and insertion /deletion loops.
Base excision repair and mismatch repair are two different mechanisms involved in DNA repair. They operate on distinct types of DNA damage and play crucial roles in maintaining the integrity of the genome.
Key Areas Covered
1. What is Base Excision Repair
– Definition, Features, Function
2. What is Mismatch Repair
– Definition, Features, Function
3. Similarities Between Base Excision Repair and Mismatch Repair
– Outline of Common Features
4. Difference Between Base Excision Repair and Mismatch Repair
– Comparison of Key Differences
Key Terms
Base Excision Repair, Mismatch Repair
What is Base Excision Repair
Base excision repair (BER) is a fundamental mechanism employed by cells to repair damaged or incorrect bases in DNA. It is a critical pathway for maintaining the integrity and stability of the genome. Base excision repair plays a vital role in preventing mutations.
DNA strands break, and the accumulation of DNA damage can lead to various diseases, including cancer. The process of base excision repair begins with the recognition and removal of damaged or incorrect bases in DNA. Various types of DNA lesions, such as oxidative damage, deamination, and alkylation, can occur due to endogenous metabolic processes or exposure to external agents like radiation or chemicals. These lesions can disrupt the normal base pairing and compromise the stability of the DNA molecule. Base excision repair acts as a surveillance and repair system to identify and correct these aberrant bases.
Steps in Base Excision Repair
The first step in base excision repair involves the recognition and excision of the damaged base. Specialized DNA glycosylases are responsible for recognizing specific types of lesions. These glycosylases have substrate specificity and can distinguish normal bases from damaged ones. Once a damaged base is recognized, DNA glycosylase cleaves the glycosidic bond between the damaged base and the sugar-phosphate backbone, resulting in the removal of the base. This creates an apurinic/apyrimidinic site or abasic site.
The second step of BER involves the processing of the AP site. AP endonucleases recognize the AP site and cleave the DNA backbone at the site of the lesion, generating a DNA gap with a 5’-deoxyribose phosphate moiety. The resulting gap is then ready for repair synthesis.
The third step of BER is repair synthesis, where the gap is filled with the correct nucleotides. DNA polymerases, such as DNA polymerases beta in humans, catalyze the synthesis of a new DNA strand complementary to the template strand. The polymerase incorporates the correct nucleotides using the undamaged DNA strand as a template, effectively restoring the missing bases.
Following repair synthesis, the final step of BER involves sealing the newly synthesized DNA strand to the original DNA molecule. DNA ligases, such as DNA ligase III in humans, catalyze the formation of a phosphodiester bond between the 3’-hydroxyl group of the DNA backbone and the 5’ -phosphate group, sealing the nick and completing the repair process.
Several accessory proteins and enzymes participate in coordinating and regulating the different steps of BER. These include DNA damage sensors, scaffold proteins, DNA binding proteins, and additional enzymes involved in the processing of DNA ends, gap filling, and ligation. The coordination and interplay between these factors ensure the accurate and efficient repair of damaged bases.
What is Mismatch Repair
Mismatch repair is a vital cellular mechanism that safeguards genomic integrity and prevents the accumulation of mutations. DNA replication errors, as well as DNA damage induced by exogenous factors, can result in mismatches, insertions, or deletions in the DNA sequence. Mismatch repair systems serve as proofreading mechanisms, correcting these errors to maintain genetic stability. The main function of mismatch repair is to prevent the accumulation of mutations in the genome. By correcting the DNA replication errors and damage-induced mismatches, mismatch repair pathways help maintain the fidelity of DNA replication. Defects in the mismatch repair machinery can lead to an increased mutation rate resulting in genomic instability and a higher predisposition to cancer.
Mismatch repair involves a complex set of proteins that work in a coordinated manner to identify and rectify errors in DNA. The key players in this process include mismatch recognition proteins such as MutSalpha and MutSbeta and the downstream repair proteins MutLalpha and exonucleases.
The first step of mismatch repair is the recognition of the mismatched base pairs. Mutsalpha recognizes the base-base mismatches and small insertion-deletion loops, while MutSbeta targets larger insertion-deletion loops. Upon recognition, MutS proteins recruit Mutlalpha to form a repair complex at the site of the mismatch. This complex acts as a molecular scaffold to coordinate subsequent repair steps. Mismatch repair also involves the action of exonucleases, such as exonuclease 1, which removes the erroneous DNA strand starting from the mismatch site. The gap left by exonuclease activity is then filled by DNA polymerase and sealed by DNA ligase, effectively restoring the correct DNA sequence.
Similarities Between Base Excision Repair and Mismatch Repair
- Base excision repair and mismatch repair are involved in the recognition of specific DNA lesions or abnormalities.
- Both repair pathways rely on a set of specialized proteins to carry out their respective functions.
- Both mechanisms involve the ability to discriminate between the template and newly synthesized DNA strands.
Difference Between Base Excision Repair and Mismatch Repair
Definition
Base excision repair is a cellular mechanism that corrects damaged or incorrect bases in DNA by removing the damaged base and replacing it with the correct one, while mismatch repair is a cellular process that identifies and repairs errors in DNA caused by mispaired nucleotides, ensuring the accuracy of DNA replication and preventing mutation.
Function
Base excision repair is mainly responsible for repairing small non-bulky lesions in DNA, such as damaged or incorrect bases as well as single strand breaks, whereas mismatch repair is mainly responsible for correcting errors that occur during DNA replication, including mismatches and insertion /deletion loops.
Timing of Repair
While base excision repair can occur both during DNA replication and non-replicating cells, mismatch repair mainly operates during DNA replication.
Proteins Involved
Base excision repair relies on specific enzymes, including DNA glycosylases, endonucleases, DNA polymerases, and DNA ligases, to execute the repair process, while mismatch repair involves the action of MutS and MulL protein complexes along with other associated proteins to recognize, excise, and repair mismatches and insertion/deletion loops.
Conclusion
The main difference between base excision repair and mismatch repair is that base excision repair is mainly responsible for repairing small non-bulky lesions in DNA, such as damaged or incorrect bases and single-strand breaks, whereas mismatch repair is mainly responsible for correcting errors that occur during DNA replication, including mismatches and insertion /deletion loops.
Reference:
1. “Base Excision Repair, a Pathway Regulated by Posttranslational Modifications.” National Library of Medicine.
2. “DNA Mismatch Repair – An Overview.” Science Direct.
Image Courtesy:
1. “Base excision repair” By Allen Gathman (CC BY-NC-SA 2.0) via Flickr
2. “DNA Mismatch Repair 4” By Allen Gathman (CC BY-NC-SA 2.0) via Flickr
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