To be or not to be: regulation of restriction–modification systems and other toxin–antitoxin systems

Abstract

One of the simplest classes of genes involved in programmed death is that containing the toxin–antitoxin (TA) systems of prokaryotes. These systems are composed of an intracellular toxin and an antitoxin that neutralizes its effect. These systems, now classified into five types, were initially discovered because some of them allow the stable maintenance of mobile genetic elements in a microbial population through postsegregational killing or the death of cells that have lost these systems. Here, we demonstrate parallels between some TA systems and restriction–modification systems (RM systems). RM systems are composed of a restriction enzyme (toxin) and a modification enzyme (antitoxin) and limit the genetic flux between lineages with different epigenetic identities, as defined by sequence-specific DNA methylation. The similarities between these systems include their postsegregational killing and their effects on global gene expression. Both require the finely regulated expression of a toxin and antitoxin. The antitoxin (modification enzyme) or linked protein may act as a transcriptional regulator. A regulatory antisense RNA recently identified in an RM system can be compared with those RNAs in TA systems. This review is intended to generalize the concept of TA systems in studies of stress responses, programmed death, genetic conflict and epigenetics.

Diversity of Integrative and Conjugative Elements of Streptococcus salivarius and Their Intra- and Interspecies Transfer

“…RM systems that carry the restriction enzyme activity and modification enzyme activity on separate proteins (as observed for the ICEs of the ICESt3 subfamily) can have an impact on the maintenance of the MGEs carrying them (mechanism of genetic addiction). The MGE encodes the poison endonuclease activity and its "antidote," the methyltransferase (37). Postsegregational killing would occur if the whole RM system was lost.…”

Bacteriophage Orphan DNA Methyltransferases: Insights from Their Bacterial Origin, Function, and Occurrence

“…In such cases, R-M systems may behave "selfishly" if the incoming parasitic DNA gains access to the host cell. Displacement of the R-M systems in members of the populations may cause the cells to die, a process known as postsegregational killing, a similar mechanism of plasmid maintenance that occurs with toxin-antitoxin systems (24)(25)(26). The daughter cells are no longer protected due to a reduction in methylation activity, and their genetic material is subjected to cleavage by the still present REase (27).…”

Regulation of genetic flux between bacteria by restriction–modification systems

“…They encode a methyltransferase (MTase) function that modifies particular DNA sequences in function of the presence of target recognition sites and a restriction endonuclease (REase) function that cleaves them when they are unmethylated (5). R-M systems are traditionally classified into three main types.…”