Strand discrimination in DNA mismatch repair (bacteria) During post-replicative mismatch repair in many bacteria, how are newly synthesized DNA strands distinguished from the parental strands?

Introduction / Context:
Mismatch repair (MMR) corrects replication errors that escape polymerase proofreading. In bacteria such as E. coli, the system must identify which strand carries the newly introduced error and which is the correct template. Strand discrimination is essential to fix the right base.

Given Data / Assumptions:

• Hemimethylation occurs immediately after replication.
• Dam methylase methylates adenines in GATC sites on the parental strand first.
• MMR proteins recognize methylation status to direct repair.

Concept / Approach:
Right after replication, the parental strand is methylated at GATC sites, while the nascent strand is not yet methylated. The MutS/MutL/MutH system targets the unmethylated (new) strand for incision and resynthesis, thereby correcting the mismatch using the methylated parental strand as the template.

Step-by-Step Solution:
Recognize hemimethylated DNA as the post-replication state.Identify which strand is methylated: the older template.Conclude MMR discriminates using methylation marks, targeting the unmethylated new strand.Select the option describing “old methylated, new unmethylated.”

Verification / Alternative check:
Mutations in dam methylase or MutHLS components disrupt strand discrimination and elevate mutation rates, validating the mechanism.

Why Other Options Are Wrong:

• Absence of cytosine or molecular size differences are unrelated to MMR marking.
• New strands methylated while old are not: reverses the biological reality.
• Ribonucleotide incorporation is not a normal discrimination signal.

Common Pitfalls:
Confusing eukaryotic MMR cues (e.g., nicks on the lagging strand) with bacterial methyl-directed MMR; mechanisms differ across domains.

Final Answer:
Old (template) strands are methylated while the new strands are initially unmethylated (hemimethylated DNA).