The mismatch repair pathway recognizes and repairs errors that occur during DNA replication and recombination, helping maintain genomic stability. It increases the accuracy of DNA replication in E. coli by 20-400 fold. There are two types of mismatch repair mechanisms, one used by most eukaryotes and bacteria and the other specific to E. coli. The MutS protein is key to this pathway as it detects mismatches in double-stranded DNA and initiates the repair machinery through nonspecific interactions. It has two domains that change conformation upon recognizing DNA lesions or binding to DNA to affect each other's function.

1. Mismatch Repair Pathway
DNA mismatch repair (MMR) recognizes and repairs erroneous insertion, deletion,
and mis-incorporation of bases that can arise during DNA replication and
recombination, and repair some forms of DNA damage. It plays an important role in
maintaining genomic stability and cellular homeostasis. For example, MMR increases
the accuracy of DNA replication by 20–400-fold in Escherichia coli. The mismatch
repair machinery distinguishes the newly synthesised strand from the template
(parental) to begin the repair process. Nowadays, 2 types of MMR mechanisms have
been demonstrated, one is expected to be employed by eukaryotes and the majority
of bacteria, and the other is specific to E. coli and some bacteria.
MutS is the pivotal protein of the MMR system that can detect mismatches in the
double-stranded DNA. It initiates the MMR machinery by recognizing nonspecific
interactions. It has two functional domains including a DNA-binding domain and an
ATPase/dimerization domain. Both domains of the MutS protein are sterically distant
in the inactive state, but conformation changes on recognizing a specific lesion in
DNA, ATP or just binding to DNA. Both protein domains affect each others’ function.
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