A non-canonical mismatch repair pathway in prokaryotes

A. Castañeda-García, A. I. Prieto, J. Rodríguez-Beltrán, N. Alonso, D. Cantillon, C. Costas, L. Pérez-Lago, E. D. Zegeye, M. Herranz, P. Plociński, T. Tonjum, D. García de Viedma, M. Paget, S. J. Waddell, A. M. Rojas (), A. J. Doherty () and J. Blázquez ()
Additional contact information
A. Castañeda-García: Stress and Bacterial Evolution Group, Instituto de Biomedicina de Sevilla. Avda. Manuel Siurot S/N
A. I. Prieto: Stress and Bacterial Evolution Group, Instituto de Biomedicina de Sevilla. Avda. Manuel Siurot S/N
J. Rodríguez-Beltrán: Stress and Bacterial Evolution Group, Instituto de Biomedicina de Sevilla. Avda. Manuel Siurot S/N
N. Alonso: Centro Nacional de Biotecnología-CSIC. C/ Darwin 3
D. Cantillon: Brighton and Sussex Medical School, University of Sussex
C. Costas: Stress and Bacterial Evolution Group, Instituto de Biomedicina de Sevilla. Avda. Manuel Siurot S/N
L. Pérez-Lago: Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital Gregorio Marañón and Instituto de Investigación Sanitaria Gregorio Marañón. Dr. Esquerdo 46
E. D. Zegeye: Oslo University Hospital, Rikshospitalet, Oslo, University of Oslo
M. Herranz: Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital Gregorio Marañón and Instituto de Investigación Sanitaria Gregorio Marañón. Dr. Esquerdo 46
P. Plociński: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex
T. Tonjum: Oslo University Hospital, Rikshospitalet, Oslo, University of Oslo
D. García de Viedma: Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital Gregorio Marañón and Instituto de Investigación Sanitaria Gregorio Marañón. Dr. Esquerdo 46
M. Paget: School of Life Sciences, University of Sussex
S. J. Waddell: Brighton and Sussex Medical School, University of Sussex
A. M. Rojas: Computational Biology and Bioinformatics, Instituto de Biomedicina de Sevilla (IBIS)-CSIC. Avda. Manuel Siurot S/N
A. J. Doherty: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex
J. Blázquez: Stress and Bacterial Evolution Group, Instituto de Biomedicina de Sevilla. Avda. Manuel Siurot S/N

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14246

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