Editing Integrase (section)

=== Integration mechanism ===
Following synthesis of HIV's doubled stranded DNA genome, integrase binds to the long tandem repeats flanking the genome on both ends. Using its endonucleolytic activity, integrase cleaves a di or trinucleotide from both 3' ends of the genome in a processing known as 3'-processing.<ref name=":3">{{cite journal | vauthors = Mahboubi-Rabbani M, Abbasi M, Hajimahdi Z, Zarghi A | title = HIV-1 Reverse Transcriptase/Integrase Dual Inhibitors: A Review of Recent Advances and Structure-activity Relationship Studies | journal = Iranian Journal of Pharmaceutical Research | volume = 20 | issue = 2 | pages = 333–369 | date = 2021 | pmid = 34567166 | doi = 10.22037/ijpr.2021.115446.15370 | pmc = 8457747 }}</ref> The specificity of cleavage is improved through the use of cofactors such as Mn<sup>2+</sup> and Mg<sup>2+</sup> which interact with the DDE motif of the catalytic core domain, acting as cofactors to integrase function.<ref name=":3" />

The newly generated 3'OH groups disrupt the host DNA's [[phosphodiester linkage]]s through SN2-type nucleophilic attack.<ref name=":2" /> The 3' ends are covalently linked to the target DNA. The 5' over hangs of the viral genome are then cleaved using host repair enzymes, those same enzymes are believed to be responsible for the integration of the 5' end into the host genome forming the provirus.<ref name=":2" /><ref name=":3" />