The fate of the discontinuous viral DNA duplex synthesized in the cytosol of an infected cell by HIV-1 reverse transcriptase is not entirely clear. Studies of some viral systems suggest that this discontinuous structure is required for passage of the viral duplex DNA into the nucleus while there are evidence contrary to this observation. Studies in vitro indicate that human nuclear flap endonuclease and DNA ligase can remove the flap and seal the plus-strand discontinuity in HIV-1 DNA (Miller et al. 1995; Rausch and Le Grice 2004; Rumbaugh et al. 1998), although role of flap is not yet clear.