Cell death upon epigenetic genome methylation: a novel function of methyl-specific deoxyribonucleases

Abstract

Background: Alteration in epigenetic methylation can affect gene expression and other processes. In Prokaryota, DNA methyltransferase genes frequently move between genomes and present a potential threat. A methyl-specific deoxyribonuclease, McrBC, of Escherichia coli cuts invading methylated DNAs. Here we examined whether McrBC competes with genome methylation systems through host killing by chromosome cleavage.

Diverse Functions of Restriction-Modification Systems in Addition to Cellular Defense

“…The selfish gene model explains the phenomenon that type II R-M systems could not be lost due to random fluctuations in plasmid segregation. Host cell killing was also shown with the type IV enzyme McrBC by the introduction of a DNA methylation gene (96). Although such selfish behavior appears to be a widespread phenomenon with type II R-M systems, it is not common in type I or III enzymes (97).…”

“…However, a direct role for R-M systems in cell death mechanisms has not been reported. Recent work by Kobayashi's group provided evidence for a new function of the methyl-specific endodeoxyribonuclease McrBC (96). In that study, McrBC of E. coli was shown to limit the invasion of exogenous methyltransferase by host cell death (96).…”

“…Postsegregational killing is triggered by REases belonging to type II R-M systems when methylation by the cognate MTase is decreased (see "Selfish Genes"). Type IV enzymes maintain the genome methylation status by initiating cell death when an additional foreign genome encoding an MTase gene enters the cell (96). Thus, cell death caused by type I, II, and IV systems in host bacteria exhibiting lower-level or altered methylation would ensure the maintenance of the epigenetic status in the remaining clonal population.…”

“…Recent work by Kobayashi's group provided evidence for a new function of the methyl-specific endodeoxyribonuclease McrBC (96). In that study, McrBC of E. coli was shown to limit the invasion of exogenous methyltransferase by host cell death (96). Interestingly, in the absence of exogenous methylation, the type IV REase Mrr enzymes of E. coli and S. Typhimurium were shown to restrict their own genomes under stress conditions (219,220), indicating a cellular role distinct from the classical defense function of R-M systems.…”

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

“…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). An example of this phenomenon is the chromosomally encoded BamHI R-M system of Bacillus amyloliquefaciens, which was shown to resist replacement by homologous recombination (28).…”