RT Journal Article T1 A non-canonical mismatch repair pathway in prokaryotes. A1 Castañeda-Garcia, A A1 Prieto, A I A1 Rodriguez-Beltran, J A1 Alonso, N A1 Cantillon, D A1 Costas, C A1 Perez-Lago, L A1 Zegeye, E D A1 Herranz, M A1 Plociński, P A1 Tonjum, T A1 Garcia-de-Viedma, D A1 Paget, M A1 Waddell, S J A1 Rojas, A M A1 Doherty, A J A1 Blazquez, J K1 DNA mismatch repair K1 Microbial genetics K1 Phylogenetics AB Mismatch repair (MMR) is a near ubiquitous pathway, essential for the maintenance of genome stability. Members of the MutS and MutL protein families perform key steps in mismatch correction. Despite the major importance of this repair pathway, MutS-MutL are absent in almost all Actinobacteria and many Archaea. However, these organisms exhibit rates and spectra of spontaneous mutations similar to MMR-bearing species, suggesting the existence of an alternative to the canonical MutS-MutL-based MMR. Here we report that Mycobacterium smegmatis NucS/EndoMS, a putative endonuclease with no structural homology to known MMR factors, is required for mutation avoidance and anti-recombination, hallmarks of the canonical MMR. Furthermore, phenotypic analysis of naturally occurring polymorphic NucS in a M. smegmatis surrogate model, suggests the existence of M. tuberculosis mutator strains. The phylogenetic analysis of NucS indicates a complex evolutionary process leading to a disperse distribution pattern in prokaryotes. Together, these findings indicate that distinct pathways for MMR have evolved at least twice in nature. PB Nature Publishing Group YR 2017 FD 2017-01-27 LK http://hdl.handle.net/10668/10811 UL http://hdl.handle.net/10668/10811 LA en NO Castañeda-García A, Prieto AI, Rodríguez-Beltrán J, Alonso N, Cantillon D, Costas C, et al. A non-canonical mismatch repair pathway in prokaryotes. Nat Commun. 2017 Jan 27;8:14246. DS RISalud RD Apr 6, 2025