Collectively the data about dnd system, have led us to propose that Dnd sulphur-based modification constitutes a novel DNA uptake barrier system reminiscent of the widely studied and highly diverse RM (restriction-modification)-systems present in almost all bacterial species characterized to date. Briefly, an RM-system consists of a restriction enzyme(s) that cleave DNA and a methylase enzyme that modifies a particular base within or adjacent to the sequence that the restriction enzyme cleaves.

The highly specific nature of methylation protects DNA from digestion by the cognate restriction enzyme. When unmodified bacteriophage, plasmid or stray DNA enters a bacterium that possesses a RM-system, the restriction enzyme of the host cell is unhindered and proceeds to degrade the invading DNA, thus providing a major barrier to DNA uptake.

The Dnd system exhibits strong parallels with RM systems: sequence-specific modification of DNA, genes present on genomic islands, reduced transfer of DNA modification genes into otherwise receptive hosts, and most strikingly, the presence of a putative endonuclease that is hypothesized to specifically cleave Dnd-modified DNA.
Fig. 1. Comjugation experiment showed that dnd cluster from Streptomyces lividans 1326 was very hard to be introduced into its close relative S. coelicolor M145. when dnd cluster has a addition G insertion, presented as dnd*, the conjugation efficiency for dnd* can be 10^4 higher than the wild type. This observation suggests a modification-dependent restriction system in S. coelicolor M145.

G. Liu, H.Y. Ou, T. Wang, L. Li, H. Tan, X. Zhou, K. Rajakumar, Z. Deng and X. He (2010) Cleavage of Phosphothioated DNA and Methylated DNA by the Type IV Restriction Endonuclease ScoMcrA. PLoS Genetics, 6(12): e1001253. [Abstract]