The mismatch-repair activity of E. coil repairs misincorporated bases which is not removed by the proofreading activity of DNA polymerase. However, while doing so, it has to decide which strand of the DNA is newly synthesized and which one is parental. Mismatch repair system does it by which one of the following ways?
(1) It recognizes nearby GATC sequence.
(2) It recognizes any nearby palindromic sequence.
(3) It recognizes a specific repetitive sequence.
(4) It recognizes the hemi-methylated GATC sequence nearby.

How the Mismatch Repair System in E. coli Identifies the Newly Synthesized DNA Strand: The Role of Hemi-Methylated GATC Sequences

DNA replication is a remarkably accurate process, but errors occasionally occur when the DNA polymerase incorporates the wrong base. While the proofreading activity of DNA polymerase corrects most mistakes, some misincorporated bases escape detection and become mismatches in the DNA. To address these errors, Escherichia coli (E. coli) employs a sophisticated system called mismatch repair (MMR). A critical challenge for MMR is distinguishing the newly synthesized (daughter) strand—which contains the error—from the original (parental) strand. This article explains how E. coli achieves this, explores the correct answer, and provides SEO-optimized content with relevant keywords.

Understanding Mismatch Repair in E. coli

Mismatch repair (MMR) is a highly conserved DNA repair pathway that corrects errors introduced during DNA replication, recombination, and certain types of chemical damage. In E. coli, MMR is essential for maintaining genomic stability and preventing mutations that could lead to diseases such as cancer137.

Key Features of MMR

• Strand-Specific Repair: MMR must remove the misincorporated base from the newly synthesized (daughter) strand, not the parental (template) strand.

• Enzymes Involved: The core MMR machinery in E. coli includes MutS (recognizes mismatches), MutL (signals the repair process), MutH (nuclease that cleaves the daughter strand), and UvrD (helicase that unwinds DNA).

• Broad Substrate Specificity: MMR can correct base-base mismatches and small insertion/deletion loops27.

The Challenge: Strand Discrimination

A fundamental problem in MMR is strand discrimination—how to identify which strand contains the error and should be removed and resynthesized. If the wrong strand is repaired, the mutation would be permanently incorporated into the genome137.

How Does E. coli Solve This Problem?

In E. coli, the answer lies in DNA methylation. The bacterial genome contains specific sequences called GATC sites that are methylated on the adenine (A) residue. However, after DNA replication, the newly synthesized strand is not immediately methylated, resulting in hemi-methylated DNA—a GATC site where only the parental strand is methylated347.

The Role of MutH

The MutH protein is a site-specific endonuclease that recognizes hemi-methylated GATC sites. When MutS and MutL identify a mismatch, they recruit MutH to a nearby hemi-methylated GATC site. MutH then cleaves the unmethylated (newly synthesized) strand, marking it for removal37.

Excision and Resynthesis

Following strand cleavage, exonucleases and helicases excise the segment of the newly synthesized strand containing the mismatch. DNA polymerase then resynthesizes the correct sequence using the parental strand as a template, and DNA ligase seals the nick27.

Why Other Options Are Incorrect

• Option (1): It recognizes nearby GATC sequence.

  • Incorrect: The MMR system does not simply recognize any GATC sequence; it specifically targets hemi-methylated GATC sites to distinguish the newly synthesized strand347.

• Option (2): It recognizes any nearby palindromic sequence.

  • Incorrect: Palindromic sequences are not involved in strand discrimination for MMR.

• Option (3): It recognizes a specific repetitive sequence.

  • Incorrect: Repetitive sequences are not the signal for strand discrimination in E. coli MMR.

• Option (4): It recognizes the hemi-methylated GATC sequence nearby.

  • Correct: The MMR system identifies the newly synthesized strand by recognizing hemi-methylated GATC sites, where only the parental strand is methylated347.

The Correct Answer

Option (4): It recognizes the hemi-methylated GATC sequence nearby.

Importance of Strand Discrimination in MMR

Accurate strand discrimination is essential for the fidelity of DNA replication. If the MMR system cannot distinguish the newly synthesized strand, it might mistakenly repair the parental strand, leading to permanent mutations. The use of hemi-methylated GATC sites ensures that only the strand containing the replication error is corrected, preserving genomic integrity137.

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• DNA replication errors

• Proofreading activity of DNA polymerase

• DNA repair mechanisms

• Genomic stability

• MutH endonuclease

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• GATC site in DNA repair

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• DNA repair enzymes

• DNA replication fidelity

Conclusion

The mismatch repair system of E. coli repairs misincorporated bases that escape the proofreading activity of DNA polymerase. To ensure the correct strand is repaired, the system recognizes hemi-methylated GATC sequences nearby the mismatch, marking the newly synthesized strand for removal and resynthesis. The correct answer is option (4): It recognizes the hemi-methylated GATC sequence nearby. This mechanism is crucial for maintaining the accuracy of DNA replication and preventing mutations.