The Daily Bulletin

Dr. Gayan Senavirathne from the Memorial Sloan Kettering Cancer Center will give a research seminar on Thursday, March 20, 2025, from 12:15 PM to 1:30 PM in SAMC 151.

Seminar Title: DNA Gaps promote targeted retroviral integration

Abstract:

Integration into the host genome is a crucial step in retrovirus infection, catalyzed by an intasome composed of viral integrase (IN) and reverse-transcribed (RT) copy DNA (cDNA). Previous studies have shown that DNA site recognition constrains intasome integration. Using single-molecule Förster resonance energy transfer (smFRET), we demonstrate that Prototype Foamy Virus (PFV) intasomes preferentially bind and pause at DNA strand breaks and gaps. These discontinuities resemble base excision repair (BER) lesion-processing intermediates, which are known to influence retroviral integration in vivo. Intasome pausing at these sites facilitates site-directed integration without inducing significant conformational changes. In contrast, the BER substrate 8-Oxoguanine and a G/T mismatch or a +T nucleotide insertion, introducing flexibility or bending in the DNA backbone, did not enhance intasome pausing or targeted integration. These findings suggest that DNA repair intermediates play a role in modulating intasome dynamics and directing retroviral integration.