Escalante Lab

Virginia Commonwealth University

PHYSIOLOGY

Richmond · United States

NIH-funded
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NIH R01 · 2024

Structural and Mechanistic Insights into AAV Rep Mediated Site-Specific Integration and Packaging

PROJECT SUMMARY Adeno-Associated Virus (AAV) has evolved the property to integrate into its host genome exploiting a unique mechanism shared by organisms in all domains of life to process single stranded DNA during DNA replication, bacterial conjugation and special cases of transposition. The large AAV Rep proteins Rep68/Rep78 are the key players that carry out this process using two multifunctional domains that include an origin binding domain (OBD) that binds DNA specifically and belongs to the family of HUH endonucleases; and a SF3 helicase domain. Integration is contingent on the binding of Rep68/Rep78 to the integration site AAVS1, promote its melting and perform a strand-specific…

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