A non-canonical mismatch repair pathway in prokaryotes

Abstract

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.

High‐quality draft genome sequence of Gaiella occulta isolated from a 150 meter deep mineral water borehole and comparison with the genome sequences of other deep‐branching lineages of the phylum Actinobacteria

“…Gaiella occulta genome sequence has the key enzymes for the main DNA repair mechanisms, except for the mismatch repair pathway. Genes mutS and mutL were not encountered, as in many Actinobacteria and Archaea (Castañeda‐García et al, ). A gene coding for the endonuclease NucS (Gocc_1770) was identified, suggesting G. occulta may use the noncanonical mismatch repair pathway described recently for Mycobacterium smegmatis and Streptomyces coelicolor (Castañeda‐García et al, ).…”

“…Genes mutS and mutL were not encountered, as in many Actinobacteria and Archaea (Castañeda‐García et al, ). A gene coding for the endonuclease NucS (Gocc_1770) was identified, suggesting G. occulta may use the noncanonical mismatch repair pathway described recently for Mycobacterium smegmatis and Streptomyces coelicolor (Castañeda‐García et al, ). Thermoleophilum album and S. soli may also use this alternative mismatch repair pathway as they also lack homologs of mutS and mutL and have a nucS homolog.…”

The mismatch repair system (mutS and mutL) in Acinetobacter baylyi ADP1

“…The homologues of MutS exist in all prokaryotes, with the exception of Actinobacteria, Mollicutes and part of the Archaea [11]. Bacteria of the Actinobacteria Phylum and Archaea encode a non-canonical MMR system (NucS/endoMS) [12]. For Mollicutes, it was reported that the histone-like protein HU (Hup2) in M. gallisepticum might play it role in mismatch repair [13].…”

RecGwed: A probable novel regulator in the resolution of branched DNA structures in mycobacteria

“…Mycobacterial DNA repair is an under‐explored area, mostly understood in terms of homology . However, recent studies in the field of DNA repair have revealed the presence of several novel proteins and pathways in mycobacteria . A previous analysis of the mycobacterial genomes, in our laboratory, revealed the presence of a protein RecG wed , with a standalone wedge domain .…”