MutS

MutS is a DNA mismatch repair protein found in bacteria and archaea, and a member of the MutS family of proteins that maintain genetic stability. It recognizes base–base mismatches and insertion/deletion loops created during DNA replication and helps direct repair toward the newly synthesized strand. In many bacteria, MutS functions as a homodimer that binds to a mismatch and facilitates the recruitment of MutL to form a repair complex. In Escherichia coli, this complex interacts with MutH, an endonuclease that introduces a nick on the unmethylated daughter strand near a GATC site, enabling excision of the error-containing segment and subsequent gap filling and ligation. Some bacteria repair mismatches through MutL-mediated nicking without a MutH homolog, illustrating variation in the bacterial MutS-centric repair pathway.

MutS contains multiple functional domains. An N-terminal mismatch-recognition domain detects incorrect base pairing, followed by core and clamp-like regions that stabilize DNA binding and coordinate interactions with MutL. The C-terminal ATPase domain binds and hydrolyzes ATP, a catalytic feature that drives conformational changes and modulates the sliding and signaling functions of MutS along DNA. ATP binding and hydrolysis promote the transition between distinct conformations needed for effective mismatch signaling and recruitment of downstream repair factors.

Genetically, mutS is essential for high-fidelity DNA replication; loss-of-function mutations produce a mutator phenotype with elevated spontaneous mutation rates. The gene is widely conserved among bacteria and archaea. Eukaryotes harbor MutS homologs (such as MSH2 paired with MSH6 or MSH3) that perform analogous mismatch repair roles in the nucleus, reflecting the evolutionary conservation of this critical repair pathway.