The endonucleases from the Type IIB restriction–modification systems differ from all other restriction enzymes. The Type IIB enzymes cleave both DNA strands at specified locations distant from their recognition sequences, like Type IIS nucleases, but they are unique in that they do so on both sides of the site, to liberate the site from the remainder of the DNA on a short duplex. The fact that these enzymes cut DNA at specific locations mark them as Type II systems, as opposed to the Type I enzymes that cut DNA randomly, but in terms of gene organization and protein assembly, most Type IIB restriction–modification systems have more in common with Type I than with other Type II systems. Our current knowledge of the Type IIB systems is reviewed in the present paper.

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