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Retroviral intasomes search for a target DNA by 1D diffusion which rarely results in integration
- Retroviral intasomes search for a target DNA by 1D diffusion which rarely results in integration
- Jones, N.D., Lopez, M.A., Jr., Hanne, J., Peake, M.B., Lee, J.-B., Fishel, R., Yoder, K.E.; 이종봉
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- Nature communications
- Nature publishing group
- Retroviruses must integrate their linear viral cDNA into the host genome for a productive infection. Integration is catalysed by the retrovirus-encoded integrase (IN), which forms a tetramer or octamer complex with the viral cDNA long terminal repeat (LTR) ends termed an intasome. IN removes two 3'-nucleotides from both LTR ends and catalyses strand transfer of the recessed 3'-hydroxyls into the target DNA separated by 4-6 bp. Host DNA repair restores the resulting 5'-Flap and single-stranded DNA (ssDNA) gap. Here we have used multiple single molecule imaging tools to determine that the prototype foamy virus (PFV) retroviral intasome searches for an integration site by one-dimensional (1D) rotation-coupled diffusion along DNA. Once a target site is identified, the time between PFV strand transfer events is 470 ms. The majority of PFV intasome search events were non-productive. These observations identify new dynamic IN functions and suggest that target site-selection limits retroviral integration.
- PROTOTYPE FOAMY VIRUS, HIV-1 INTEGRATION, MAGNETIC TWEEZERS, SUPERCOILED DNA, MISMATCHED DNA, PROTEIN, SINGLE, SITES, NUCLEOSOMES, KINETICS
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