Which Enzyme Defects Impair the Correction of DNA Replication Errors Not Caught by Proofreading? Understanding Mismatch Repair and Related Pathways

DNA replication is a remarkably accurate process, but even the best proofreading activity of DNA polymerase occasionally lets errors slip through. To correct these mistakes, cells rely on specialized DNA repair pathways. Defects in specific enzymes involved in these pathways can impair the cell’s ability to maintain genomic stability. This article explains which enzymes are crucial for correcting replication errors, explores the correct answer, and provides SEO-optimized content with relevant keywords.

DNA Replication and Proofreading

During DNA replication, DNA polymerase synthesizes new DNA strands and proofreads its work, removing most misincorporated bases before the next nucleotide is added61011. However, some errors escape this proofreading activity and remain as mismatches or small insertions/deletions in the newly synthesized DNA.

Specialized Repair Pathways for Replication Errors

When proofreading fails, mismatch repair (MMR) and other repair pathways step in to correct the errors and maintain genomic integrity. Mismatch repair is a highly conserved process that recognizes and fixes base-base mismatches and small insertion-deletion loops that arise during replication123.

Key Enzymes in Mismatch Repair

• MutS: Recognizes mismatches in the DNA.

• MutL: Acts as a molecular matchmaker, signaling the repair process.

• DNA polymerase III: Resynthesizes the correct DNA sequence after excision.

• DNA ligase: Seals the nick in the DNA backbone after repair synthesis259.

Defects in MutS or MutL impair mismatch repair, leading to increased mutation rates and genomic instability.

Other Repair Pathways

While mismatch repair is the primary system for correcting replication errors, other enzymes are involved in different types of DNA repair:

• AP endonuclease and DNA glycosylase: These enzymes are part of the base excision repair (BER) pathway, which repairs damaged or inappropriate bases (e.g., uracil, oxidized bases) but not mismatches introduced during replication.

• RecA and RecF: These proteins are involved in homologous recombination, which repairs double-strand breaks and other complex DNA lesions, not mismatches from replication errors.

Analysis of the Given Options

Let’s examine each option:

• A. DNA polymerase III and DNA ligase:

  • Role: DNA polymerase III resynthesizes the correct DNA after excision, and DNA ligase seals the nick. Both are essential for mismatch repair.

  • Defect Impact: Impairs mismatch repair, leading to uncorrected replication errors59.

• B. AP endonuclease and DNA glycosylase:

  • Role: Involved in base excision repair, not mismatch repair.

  • Defect Impact: Impairs BER, not the correction of replication errors missed by proofreading.

• C. MutS and MutL:

  • Role: Core components of mismatch repair.

  • Defect Impact: Impairs mismatch repair, leading to increased mutation rates234.

• D. RecA and RecF:

  • Role: Involved in homologous recombination, not mismatch repair.

  • Defect Impact: Impairs double-strand break repair, not correction of replication errors.

Which Enzyme Defects Impair the Correction of Replication Errors?

Only defects in enzymes directly involved in mismatch repair—DNA polymerase III, DNA ligase, MutS, and MutL—impair the correction of replication errors not caught by proofreading.

• AP endonuclease and DNA glycosylase (B) and RecA and RecF (D) are not involved in mismatch repair.

• DNA polymerase III and DNA ligase (A) and MutS and MutL (C) are essential for mismatch repair.

However, the question asks about the specialized repair pathways that correct replication errors not caught by proofreading, which is primarily mismatch repair. While DNA polymerase III and DNA ligase are necessary for the final steps of mismatch repair, MutS and MutL are the core recognition and signaling components specifically dedicated to initiating and directing mismatch repair234.

But in the given options, A (DNA polymerase III and DNA ligase) and C (MutS and MutL) are both involved in the overall mismatch repair process. Option (4): A and C is the most comprehensive and correct answer, as defects in both sets of enzymes impair mismatch repair and thus the correction of replication errors.

However, in most standard explanations, MutS and MutL are the primary enzymes whose defects directly impair mismatch repair initiation and signaling, while DNA polymerase III and DNA ligase are required for the completion of repair but are not unique to mismatch repair (they are also used in other repair pathways).

If the question is interpreted strictly as which enzymes’ defects impair the specialized mismatch repair pathway (as opposed to the general repair machinery), then MutS and MutL (C) are the most specific. But since both A and C are involved, and the question lists both, and given the options, the best fit is:

Option (4): A and C

But to clarify: Defects in MutS and MutL (C) are most directly responsible for impairing mismatch repair itself, while defects in DNA polymerase III and DNA ligase (A) would impair all DNA repair processes requiring synthesis and ligation, not just mismatch repair. However, since the question asks about the correction of replication errors not caught by proofreading, which is specifically the job of mismatch repair, and since both A and C are listed as options, and “A and C” is a choice, option (4): A and C is the correct answer among the provided choices.

Related Keywords for SEO Optimization

• DNA replication errors

• Proofreading activity of DNA polymerase

• Mismatch repair pathway

• MutS and MutL enzymes

• DNA polymerase III and DNA ligase

• DNA repair mechanisms

• Genomic stability

• Replication error correction

• DNA glycosylase and AP endonuclease

• RecA and RecF proteins

• Base excision repair vs mismatch repair

• DNA repair enzymes

• Defective DNA repair and mutation

• Specialized DNA repair pathways

• DNA replication fidelity

Conclusion

Defects in DNA polymerase III and DNA ligase (A) and MutS and MutL (C) impair the correction of replication errors not caught by proofreading, as these enzymes are essential for the mismatch repair pathway. AP endonuclease and DNA glycosylase (B) are involved in base excision repair, and RecA and RecF (D) are involved in homologous recombination, neither of which corrects replication errors missed by proofreading. Among the options provided, option (4): A and C is the correct answer.

However, it is important to clarify that MutS and MutL (C) are the core enzymes specific to mismatch repair, while DNA polymerase III and DNA ligase (A) are required for the final steps of repair but are not unique to mismatch repair. Nonetheless, given the choices, option (4): A and C is the most accurate answer as both sets are involved in the process of correcting replication errors through mismatch repair235.

In summary:
Correct answer: (4) A and C