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Specificity and mutagenesis bias of the mycobacterial alternative mismatch repair analyzed by mutation accumulation studies

AuthorsCastañeda-García, A.; Martín-Blecua, I.; Cebrián-Sastre, E.; Chiner-Oms, Álvaro ; Torres-Puente, Manuela ; Comas, Iñaki ; Blázquez, J.
Issue Date12-Feb-2020
PublisherAmerican Association for the Advancement of Science
CitationScience advances 6(7):eaay4453 (2020)
AbstractThe postreplicative mismatch repair (MMR) is an almost ubiquitous DNA repair essential for maintaining genome stability. It has been suggested that Mycobacteria have an alternative MMR in which NucS, an endonuclease with no structural homology to the canonical MMR proteins (MutS/MutL), is the key factor. Here, we analyze the spontaneous mutations accumulated in a neutral manner over thousands of generations by Mycobacterium smegmatis and its MMR-deficient derivative (ΔnucS). The base pair substitution rates per genome per generation are 0.004 and 0.165 for wild type and ΔnucS, respectively. By comparing the activity of different bacterial MMR pathways, we demonstrate that both MutS/L- and NucS-based systems display similar specificity and mutagenesis bias, revealing a functional evolutionary convergence. However, NucS is not able to repair indels in vivo. Our results provide an unparalleled view of how this mycobacterial system works in vivo to maintain genome stability and how it may affect Mycobacterium evolution.
Description10 páginas, 3 figuras, 3 tablas. Material suplementario en: https://advances.sciencemag.org/content/suppl/2020/02/10/6.7.eaay4453.DC1
Publisher version (URL)http://dx.doi.org/10.1126/sciadv.aay4453
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