complex remains unclear. In one version, the LEDGF/p75 binds first to the preintegration complex and then to the host DNA. On the other hand, LEDGF/p75 may bind first to the host DNA and then to the preintegration complex. Regardless of the sequence, it is believed that the presence of LEDGF/p75 results in the integrase dimers approaching each other to form a tetramer. Transfer of HIV DNA into the host DNA (Strand Transfer) The next step, the strand transfer reaction, takes place inside the host cell nucleus and involves the critical step of inserting the HIV DNA into a selected region of the host DNA. The region of insertion contains a weakly conserved palindromic sequence. This strand transfer reaction is initiated as the HIV integrase catalyzes the HIV DNA 3’-hydroxyl group attack on the host DNA. The attack by the HIV DNA occurs on opposite strands of the host DNA in a staggered fashion, typically 4-6 base pairs apart. This reaction leads to separation of the bonds in the host DNA base pairs located between the staggered cuts, and the joining of the HIV 3’-hydroxyl groups with the host DNA 5’ phosphate ends. At this point, the newly joined viral-host DNA region unfolds. Repair of the gaps formed in the strand transfer process ("Gap Repair") Following the strand transfer process, the HIV-DNA and host DNA junctions have unpaired regions of DNA, referred to as DNA "gaps". In addition, the two base pairs at the end of the 5’ region of the viral DNA remain unpaired after the strand transfer. The insertion of the new HIV DNA and the remaining gaps that flank the integration site is currently thought to induce a host cellular DNA damage response, but much of this mechanism remains speculative. The host DNA damage response is thought to be critical in the final step of integration, known as "gap repair" and may require at least three host enzymes - polymerase, nuclease, and ligase. In the first step of gap repair, it is thought that the polymerase enzyme(s) extend(s) the host DNA on each end and, thus, fill in the gaps. Next, it is possible that host nuclease activity removes the 5’ dinucleotide "flaps" on the HIV DNA. Lastly, it is thought that the DNA ligase enzymes join the remaining unbound segment of the HIV and host DNA strands. Currently this mechanism is largely validated experimentally and is an