Mismatch Repair

Some errors in DNA replication, such as incorrect base pairing between adenine and cytosine, can remain even after proofreading. Cells fix these errors after replication through a process called mismatch repair.

During mismatch repair, proteins detect distortions in DNA caused by mispaired bases. In bacteria, one of these proteins is MutS.

Other mismatch repair proteins, such as MutL, help distinguish the newly synthesized DNA strand from the original template strand, ensuring that only the incorrect strand is targeted for repair.

Different organisms identify the new DNA strand in different ways. In E. coli, the parental DNA strand is already methylated, while the newly synthesized strand remains temporarily unmethylated, allowing mismatch repair proteins to recognize and repair this new strand.

In eukaryotes, the newly synthesized DNA strand often contains small breaks, called nicks. Mismatch repair proteins recognize these nicks and target that strand.

Once the incorrect strand is identified, exonuclease enzymes remove a section of DNA that contains the error.

DNA polymerase then fills in the missing nucleotides, and DNA ligase seals the remaining gaps, restoring the correct DNA sequence.