| Autor: |
Richard Fishel, James A. London, Anne M. Gardner, Y.-Y. Tan, Ryan K. Messer, Gayan Senavirathne, Kristine E. Yoder |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.11.17.469012 |
| Popis: |
Integration into a host genome is essential for retrovirus infection and is catalyzed by a nucleoprotein complex (Intasome) containing the viral integrase (IN) and reverse transcribed (RT) copy DNA (cDNA). Previous studies demonstrated DNA site recognition limited intasome integration. Using single molecule Förster resonance energy transfer (smFRET), we show Prototype Foamy Virus (PFV) intasomes pause at DNA strand breaks and gaps. The break/gap discontinuities are similar to base excision repair (BER) lesion-processing intermediates, which affect retrovirus integration in vivo. Pausing targeted site-directed integration at the break/gap without inducing intasome conformational alterations. An 8-oxo-guanine lesion normally processes by BER and a G/T mismatch or a +T nucleotide insertion that induce flexibility or a bend in the DNA backbone did not promote intasome pausing or targeted integration. These results suggest that repair intermediates can modulate dynamic intasome-DNA interactions which target retroviral integration. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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