Integrase - Function

Function

Integration occurs following production of the double-stranded viral DNA by the viral RNA/DNA-dependent DNA polymerase reverse transcriptase.

The main function of IN is to insert the viral DNA into the host chromosomal DNA, a step that is essential 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. After integration, the viral gene expression and particle production may take place immediately or at some point in the future. The timing, it is presumed, depends on the activity of the chromosomal locus hosting the provirus.

Retroviral IN catalyzes two reactions:

• 3'-processing, in which two or three nucleotides are removed from one or both 3' ends of the viral DNA to expose the invariant CA dinucleotides at both 3'-ends of the viral DNA.
• the strand transfer reaction, in which the processed 3' ends of the viral DNA are covalently ligated to the host chromosomal DNA.

Both reactions are catalysed by the same active site and occur via transesterification, without a covalent protein-DNA intermediate, in contrast to reactions catalysed by Ser and Tyr recombinases (see site specific recombination).