Biosynthesis and Function of Modified Bases in Bacteria and Their Viruses

Abstract

Naturally occurring modification of the canonical A, G, C, and T bases can be found in the DNA of cellular organisms and viruses from all domains of life. Bacterial viruses (bacteriophages) are a particularly rich but still underexploited source of such modified variant nucleotides. The modifications conserve the coding and base-pairing functions of DNA, but add regulatory and protective functions. In prokaryotes, modified bases appear primarily to be part of an arms race between bacteriophages (and other genomic parasites) and their hosts, although, as in eukaryotes, some modifications have been adapted to convey epigenetic information. The first half of this review catalogs the identification and diversity of DNA modifications found in bacteria and bacteriophages. What is known about the biogenesis, context, and function of these modifications are also described. The second part of the review places these DNA modifications in the context of the arms race between bacteria and bacteriophages. It focuses particularly on the defense and counter-defense strategies that turn on direct recognition of the presence of a modified base. Where modification has been shown to affect other DNA transactions, such as expression and chromosome segregation, that is summarized, with reference to recent reviews.

Non‐canonical Bases in the Genome: The Regulatory Information Layer in DNA

“…These four bases,m dC,h mdC,f dC and cadC,a ll having aC atom in ad ifferent oxidation state connected to the C(5) position of the dC base,c an be considered to establish an oxidation code that has regulatory purposes.I nterestingly, some of these bases and also glycosylated versions of them, are already reported components of the genetic system in phages and bacteria. [16] Thet hree oxidised deoxycytidine bases newly discovered in mammals are now thought to be Multicellular organisms developed the concept of specialized cells that perform specific functions.E xamples are neurons and fibroblast to name just two out of more than 200. These cellular differences are established based on the same sequence information stored in the cell nucleus of all cells of an organism.…”

“…[25,26] This phage DNA modification has two effects: [27] Firstly,i tp rotects the phage DNAf rom degradation by bacterial restriction enzymes and secondly,itallows the phage to induce the production of viral endonucleases that degrade the non-modified host DNA. [16,28] In vertebrate DNA, hmdC was also discovered but only at very low levels,s ot hat it was suspected to be mostly the product of oxidative DNAd amage at the epigenetic base 5methyl-deoxycytidine (mdC,F igure 2). [29][30][31] In vitro studies, using either Fenton-type chemistry [32] (Fe 2+ /Cu 2+ ,H 2 O 2 )o r UV irradiation of mdC, [33] also in the presence of menadione as aphotosensitizer, [34] showed substantial lesion formation at mdC.…”

Identification of the minimal bacterial 2′‐deoxy‐7‐amido‐7‐deazaguanine synthesis machinery

“…More than 100 RNA modifications have been found to date (Machnicka et al, 2013), mainly in transfer RNA (tRNA) and ribosomal RNA (rRNA) (Grosjean, 2009). In contrast, only 20 modifications have been identified in DNA and most of the known DNA modifications are simple methylated derivatives of canonical nucleosides (Grosjean, 2009;Weigele and Raleigh, 2016). The few structurally complex DNA modifications are mainly found in phages where they serve to evade the host-encoded restriction systems (Warren, 1980;Weigele and Raleigh, 2016).…”

“…In contrast, only 20 modifications have been identified in DNA and most of the known DNA modifications are simple methylated derivatives of canonical nucleosides (Grosjean, 2009;Weigele and Raleigh, 2016). The few structurally complex DNA modifications are mainly found in phages where they serve to evade the host-encoded restriction systems (Warren, 1980;Weigele and Raleigh, 2016). Indeed, numerous bacteria have acquired restriction and modification (R-M) systems to defend against foreign DNA (Vasu and Nagaraja, 2013).…”

EcoBLMcrX, a classical modification-dependent restriction enzyme in Escherichia coli B: Characterization in vivo and in vitro with a new approach to cleavage site determination

“…At least 15 families of MDE have been discovered and characterized [6–8]. Some are used for study of base modification in eukaryotes (e.g.…”