Retroviral intasomes search for a target DNA by 1D diffusion which rarely results in integration
| Autor: | Jeungphill Hanne, Nathan D. Jones, Miguel Álvarez López, Jong-Bong Lee, Richard Fishel, Kristine E. Yoder, Mitchell B. Peake |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
DNA repair viruses Virus Integration Science General Physics and Astronomy DNA Single-Stranded Gene Expression Computational biology Time-Lapse Imaging General Biochemistry Genetics and Molecular Biology Article Diffusion 03 medical and health sciences chemistry.chemical_compound Viral Proteins Complementary DNA Animals Humans Genetics Multidisciplinary biology Integrases Terminal Repeat Sequences General Chemistry DNA Long terminal repeat Single Molecule Imaging Integrase 030104 developmental biology chemistry Retroviral intasome biology.protein DNA supercoil Spumavirus |
| Zdroj: | Nature Communications, Vol 7, Iss 1, Pp 1-9 (2016) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Retroviral Integration into the host DNA is a rare event with evidence suggesting that it relies on DNA topology and sequence. Here the authors present single molecule evidence that shows the retroviral integration machinery vigorously scans the target DNA by 1D-diffusion but infrequently integrates. |
| Databáze: | OpenAIRE |
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