Learning paths

Learning paths

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Learning path

Full curriculum

Full curriculum
  1. DNA replication fidelity and polymerase proofreading
  2. DNA damage and mutations as distinct genome changes
  3. DNA ligase and sealing of phosphodiester-backbone nicks
  4. Post-replicative mismatch repair

Unit content

Post-replicative mismatch repair

A copying error can escape DNA polymerase proofreading and remain as a mismatch: two chemically ordinary bases paired in a noncomplementary way, such as G-T.

Mismatch repair is a post-replicative pathway that corrects many such errors after the replication machinery has moved on.

The central challenge is not merely recognizing that the pair is abnormal. The system must also determine which strand contains the newly introduced error. If it removed the old correct nucleotide instead, it would permanently install the mistake.

Different organisms use different molecular signals to distinguish the newly synthesized strand, but the logical steps are shared.

General mechanism

  1. A repair complex recognizes abnormal base-pair geometry or a small insertion/deletion loop.
  2. The newly synthesized strand is identified.
  3. A stretch of that strand containing the mismatch is removed.
  4. DNA polymerase resynthesizes the missing segment using the intact opposite strand as a template.
  5. DNA ligase seals the remaining nick in the backbone.

Schematically:

old strand:  ... C G A T ...
new strand:  ... G T T A ...
                 ↑ mismatch

recognize new strand → excise segment → resynthesize from old strand → ligate

Why mismatch repair is distinct from proofreading

Proofreading acts at the polymerase immediately after an incorrect nucleotide is added. Mismatch repair acts later, after the polymerase has continued synthesis.

The two systems therefore form successive quality-control layers rather than alternative names for the same process.

Mismatch repair can also correct small loops created when template and new strands slip relative to one another during replication. Such loops can otherwise become small insertions or deletions.

Once an uncorrected mismatch is copied in a later round of replication, both resulting strands can form ordinary complementary pairs. At that point the repair machinery may no longer have structural evidence of which sequence was original. This is why correcting replication errors before they become fixed is essential for genome fidelity.