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Integrase
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== Function and mechanism == Integration occurs following production of the double-stranded linear viral DNA by the viral RNA/DNA-dependent DNA polymerase [[reverse transcriptase]].<ref>{{cite journal | vauthors = Burdick RC, Pathak VK | title = Efficient HIV-1 in vitro reverse transcription: optimal capsid stability is required | journal = Signal Transduction and Targeted Therapy | volume = 6 | issue = 1 | pages = 13 | date = January 2021 | pmid = 33436564 | doi = 10.1038/s41392-020-00458-3 | pmc = 7804106 }}</ref> The main function of IN is to insert the viral DNA into the host chromosomal DNA, an essential step for [[HIV]] replication. Integration is a "point of no return" for the cell, which becomes a permanent carrier of the viral genome (provirus). Integration is in part responsible for the persistence of retroviral infections.<ref>{{cite journal | vauthors = Maldarelli F | title = The role of HIV integration in viral persistence: no more whistling past the proviral graveyard | journal = The Journal of Clinical Investigation | volume = 126 | issue = 2 | pages = 438β447 | date = February 2016 | pmid = 26829624 | doi = 10.1172/JCI80564 | pmc = 4731194 }}</ref> After integration, the viral gene expression and particle production may take place immediately or at some point in the future, the timing depends on the activity of the chromosomal locus hosting the provirus.<ref name=":1" /> Retroviral INs catalyze two reactions:<ref name=":1" /> * 3'-processing, in which two or three nucleotides are removed from one or both 3' ends of the viral DNA to expose an invariant CA dinucleotide. * the strand transfer reaction, in which the processed 3' ends of the viral DNA are covalently ligated to host chromosomal DNA. Both reactions are catalyzed in the same active site, and involve [[transesterification]] without involving a [[covalent]] protein-DNA intermediate (in contrast to [[Site specific recombination|Ser/Tyr recombinase-catalyzed reactions]]).<ref name=":1" />
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