A non-canonical mismatch repair pathway in prokaryotes

Castañeda-García, A, Prieto, A I, Rodríguez-Beltrán, J, Alonso, N, Cantillon, D, Costas, C, Pérez-Lago, L, Zegeye, E D, Herranz, M, Plociński, P, Tonjum, T, García de Viedma, D, Paget, M, Waddell, S J, Rojas, A M, Doherty, A J and Blázquez, J (2017) A non-canonical mismatch repair pathway in prokaryotes. Nature Communications, 8. a14246. ISSN 2041-1723

[img] PDF - Published Version
Available under License Creative Commons Attribution.

Download (1MB)
[img] PDF - Accepted Version
Available under License Creative Commons Attribution.

Download (12MB)

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.

Item Type: Article
Keywords: antimicrobial resistance, tuberculosis, infection, DNA repair
Schools and Departments: School of Life Sciences > Biochemistry
School of Life Sciences > Sussex Centre for Genome Damage and Stability
Brighton and Sussex Medical School > Global Health and Infection
Research Centres and Groups: Genome Damage and Stability Centre
Wellcome Trust Brighton and Sussex Centre for Global Health Research
Subjects: Q Science > QR Microbiology > QR0075 Bacteria
Depositing User: Simon Waddell
Date Deposited: 06 Mar 2017 09:08
Last Modified: 22 Aug 2017 15:41
URI: http://sro.sussex.ac.uk/id/eprint/66997

View download statistics for this item

📧 Request an update
Project NameSussex Project NumberFunderFunder Ref
Molecular basis for repairing DNA double-strand breaks by non homologous end-joiningG0887-03BBSRCBB/J018643/1