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DNA phosphorothioate modification—a new multi-functional epigenetic system in bacteria

Author(s)
Wang, Lianrong; Jiang, Susu; Deng, Zixin; Dedon, Peter C; Chen, Shi
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Creative Commons Attribution NonCommercial License 4.0 https://creativecommons.org/licenses/by-nc/4.0/
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Abstract
Synthetic phosphorothioate (PT) internucleotide linkages, in which a nonbridging oxygen is replaced by a sulphur atom, share similar physical and chemical properties with phosphodiesters but confer enhanced nuclease tolerance on DNA/RNA, making PTs a valuable biochemical and pharmacological tool. Interestingly, PT modification was recently found to occur naturally in bacteria in a sequence-selective and R P configuration-specific manner. This oxygen-sulphur swap is catalysed by the gene products of dndABCDE, which constitute a defence barrier with DndFGH in some bacterial strains that can distinguish and attack non-PT-modified foreign DNA, resembling DNA methylation-based restriction-modification (R-M) systems. Despite their similar defensive mechanisms, PT- and methylation-based R-M systems have evolved to target different consensus contexts in the host cell because when they share the same recognition sequences, the protective function of each can be impeded. The redox and nucleophilic properties of PT sulphur render PT modification a versatile player in the maintenance of cellular redox homeostasis, epigenetic regulation and environmental fitness. The widespread presence of dnd systems is considered a consequence of extensive horizontal gene transfer, whereas the lability of PT during oxidative stress and the susceptibility of PT to PT-dependent endonucleases provide possible explanations for the ubiquitous but sporadic distribution of PT modification in the bacterial world.
Date issued
2018-10
URI
https://hdl.handle.net/1721.1/126286
Department
Massachusetts Institute of Technology. Department of Biological Engineering
Journal
FEMS Microbiology Reviews
Publisher
Oxford University Press (OUP)
Citation
Wong, Lianrong et al. "DNA phosphorothioate modification—a new multi-functional epigenetic system in bacteria." FEMS Microbiology Reviews, 43, 2 (March 2019): 109–122 © 2018 Oxford University Press
Version: Final published version
ISSN
1574-6976

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