ncomms14246.pdf (1.42 MB)
A non-canonical mismatch repair pathway in prokaryotes
Version 2 2023-06-12, 08:39
Version 1 2023-06-09, 05:23
journal contribution
posted on 2023-06-12, 08:39 authored by A Castañeda-García, A I Prieto, J Rodríguez-Beltrán, N Alonso, Daire Cantillon, C Costas, L Pérez-Lago, E D Zegeye, M Herranz, P Plocinski, T Tonjum, D García de Viedma, Mark PagetMark Paget, Simon WaddellSimon Waddell, A M Rojas, Aidan DohertyAidan Doherty, J BlázquezMismatch 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.
Funding
Molecular basis for repairing DNA double-strand breaks by non homologous end-joining; G0887-03; BBSRC; BB/J018643/1
History
Publication status
- Published
File Version
- Published version
Journal
Nature CommunicationsISSN
2041-1723Publisher
Nature Publishing GroupExternal DOI
Volume
8Article number
a14246Department affiliated with
- Global Health and Infection Publications
Research groups affiliated with
- Wellcome Trust Brighton and Sussex Centre for Global Health Research Publications
- Genome Damage and Stability Centre Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2017-03-06First Open Access (FOA) Date
2017-03-06First Compliant Deposit (FCD) Date
2017-03-04Usage metrics
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