title: 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.
authors.affiliation: Stress and Bacterial Evolution Group, Instituto de Biomedicina de Sevilla. Avda. Manuel Siurot S/N, 41013-Sevilla, Spain.|Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, UK.
authors.forename: A
authors.initials: A
authors.lastname: Castañeda-García
authors.affiliation: Stress and Bacterial Evolution Group, Instituto de Biomedicina de Sevilla. Avda. Manuel Siurot S/N, 41013-Sevilla, Spain.
authors.forename: A I
authors.initials: AI
authors.lastname: Prieto
authors.affiliation: Stress and Bacterial Evolution Group, Instituto de Biomedicina de Sevilla. Avda. Manuel Siurot S/N, 41013-Sevilla, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Rodríguez-Beltrán
authors.affiliation: Centro Nacional de Biotecnología-CSIC. C/ Darwin 3, 28049-Madrid, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Alonso
authors.affiliation: Brighton and Sussex Medical School, University of Sussex, Brighton BN1 9PX, UK.
authors.forename: D
authors.initials: D
authors.lastname: Cantillon
authors.affiliation: Stress and Bacterial Evolution Group, Instituto de Biomedicina de Sevilla. Avda. Manuel Siurot S/N, 41013-Sevilla, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Costas
authors.affiliation: Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital Gregorio Marañón and Instituto de Investigación Sanitaria Gregorio Marañón. Dr. Esquerdo 46, 28007-Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Pérez-Lago
authors.affiliation: Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway and Department of Microbiology, University of Oslo, P.O. Box 1072 Blindern, 0316 Oslo, Norway.
authors.forename: E D
authors.initials: ED
authors.lastname: Zegeye
authors.affiliation: Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital Gregorio Marañón and Instituto de Investigación Sanitaria Gregorio Marañón. Dr. Esquerdo 46, 28007-Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Herranz
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, UK.
authors.forename: P
authors.initials: P
authors.lastname: Plociński
authors.affiliation: Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway and Department of Microbiology, University of Oslo, P.O. Box 1072 Blindern, 0316 Oslo, Norway.
authors.forename: T
authors.identifier: 0000-0002-1709-6921
authors.initials: T
authors.lastname: Tonjum
authors.affiliation: Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital Gregorio Marañón and Instituto de Investigación Sanitaria Gregorio Marañón. Dr. Esquerdo 46, 28007-Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: García de Viedma
authors.affiliation: School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.
authors.forename: M
authors.initials: M
authors.lastname: Paget
authors.affiliation: Brighton and Sussex Medical School, University of Sussex, Brighton BN1 9PX, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Waddell
authors.affiliation: Computational Biology and Bioinformatics, Instituto de Biomedicina de Sevilla (IBIS)-CSIC. Avda. Manuel Siurot S/N, 41013-Sevilla Spain.
authors.forename: A M
authors.initials: AM
authors.lastname: Rojas
authors.affiliation: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton BN1 9RQ, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Doherty
authors.affiliation: Stress and Bacterial Evolution Group, Instituto de Biomedicina de Sevilla. Avda. Manuel Siurot S/N, 41013-Sevilla, Spain.|Centro Nacional de Biotecnología-CSIC. C/ Darwin 3, 28049-Madrid, Spain.|Unit of Infectious Diseases, Microbiology, and Preventive Medicine. University Hospital Virgen del Rocio, Avda. Manuel Siurot S/N, 41013-Sevilla, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Blázquez
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D020137:Base Pair Mismatch / Q000235:genetics; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D059645:Mutation Rate; D020102:Mycobacterium smegmatis / Q000235:genetics; D010802:Phylogeny; D048372:Streptomyces coelicolor / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004720:Endonucleases; D045643:DNA Repair Enzymes