Progress on the non-canonical mismatch repair in Mycobacterium and its role in antibiotic resistance

Mismatch repair (MMR) is a common repair system after DNA replication, which is critical for maintaining genomic stability. Members of the MutS and MutL protein families are involved in key steps of mismatch repair. Despite the major importance of this repair pathway, MutS-MutL are absent in almost all Actinobacteria and many Archaea. Mycobacteria and others have another non-canonical MMR pathway, in which EndoMS/NucS plays a key role and has no structural homology compared to canonical MMR proteins (MutS/MutL). EndoMS/NucS mediated non-canonical mismatch repair plays an important role in DNA repair, mutation, homologous recombination and antibiotic resistance of Mycobacterium. By comparing the classical and non-canonical MMR pathways, this paper reviews the EndoMS/NucS-mediated non-canonical MMR pathway in Mycobacterium and its recent progress. We hope to bring new insights into the molecular mechanism of mycobacterial mismatch repair as well as to provide new research clues for mycobacterial antibiotic therapy.