The binding of Tus to the TerB site, with an observed binding constant of 3�C10610213 M, is one of the strongest known DNA�Cprotein interactions involving a monomeric protein. The crystal structure of the Tus-Ter complex showed that Tus protein binds duplex DNA tightly through a novel two-domain structure with inter-domain b-strands and cannot be released without a large conformational change of the Tus protein. A total of 42 amino acid residues out of the 309 amino acids of Tus interact with the DNA. Of these, 18 residues lie within the bstrands, which lie partially within the major groove of the Ter DNA, and the remaining 24 residues are dispersed along the Tus protein between amino acids 50 and 302. Alterations of some of the amino acids in these domains exhibit partial or complete loss of DNA binding or DNA replication arrest activity. In mammalian cells active transport of proteins into the Mupirocin nucleus is BAR 501 impurity facilitated by the presence of a nuclear localization signal that is recognized by and associated with nuclear import receptors. Similarly, nuclear export of proteins is facilitated by the presence of a nuclear export signal, in association with an export receptor, probably CRM-1 in human cells. Although the presence of nuclear targeting sequences are common in mammalian proteins, the widely used Cre recombinase of bacteriophage P1 and VirD2 of Agrobacterium are among only a few prokaryotic proteins known to contain a sequence that functions as an NLS. However, there was no report to show that these prokaryotic proteins contain NES, in addition to NLS in the same protein. We show here with GFP fusion constructs that the E. coli Tus protein contains both NLS and NES motifs that function efficiently in human cells. Tus may be the first prokaryotic protein known to carry both nuclear import and nuclear export sequences. However, since Tus is a DNA binding protein, the presence of both NLS in Tus is probably fortuitous; and thus, the notion of biological significance would be purely speculative.