DNA modification, most often in the form of methylation, occur naturally both in prokaryotes and in eukaryotes. Subtle changes at bases, effected by proteins recognizing modified/unmodified form of specific nucleotide sequences, have profound impact on a variety of physiological aspects of related organisms. In bacteria, DNA methylation can serve as a restriction and modification system to defend the host from phage, as a genetic switch to turn specific gene expression on or off, and as a marker to coordinate chromosome replication and mismatch repair.
Although DNA backbone phosphodiester linkage is structurally monotonous, potential alterations, as a playground of chemists, have been extensively explored. DNA phosphorothioation, in which the non-bridging oxygen swapped with sulfur, is one of such effective alteration. Owing to its property of resistance to nuclease digestion, DNA phosphorothioation is widely used in biochemical and clinical applications. Interestingly, bacteria also have the ability to harvest the potential of such DNA alteration: the once proved to be sulfur containing DNA modification turns out to be DNA phosphorothioation. Physiological DNA phosphorothioation raised many questions, as noted by professor Fritz Eckstein: 1, how and why has nature chosen this particular modification? 2, what could be the mechanism of post-replicative change of phosphate to phosphorothioate? 3, how sites of DNA thiolation are chosen? 4, what are the function and advantages of this phosphorothioate modification?
Currently, I’m concentrating on the third related question: how sites of DNA phosphorothioation are chosen in bacteria?
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