title: HPV E1 up-regulates replication-related biochemistries of AAV Rep78.
abstract: Human papillomavirus type 16 (HPV) E1 protein provides helper function for the adeno-associated virus type 2 (AAV) life cycle. E1 is the replication protein of HPV, analogous to AAV Rep78, but without the endonuclease/covalent attachment activity of Rep78. Previously we have shown that E1 and Rep78 interact in vitro. Here we investigated E1's effects on Rep78 interaction with AAV's inverted terminal repeat (ITR) DNA in vitro, using purified Rep78 and E1 proteins from bacteria. E1 enhanced Rep78-ITR binding, ATPase activity, Rep78-ITR-covalent linkage and Rep78-ITR-endonuclease activity (central to AAV replication). These enhancements occurred in a dose-dependent manner whenever assayed. However, overall Rep78-plus-E1 helicase activity was lower than Rep78's helicase activity. These data suggest that E1's broad-based helper function for the AAV life cycle (AAV DNA, mRNA, and protein levels are up-regulated by E1) is likely through its ability to enhance Rep78's critical replication-required biochemistries on ITR DNA.
authors.affiliation: Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, USA.
authors.forename: Sarmistha
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Maohua
authors.initials: M
authors.lastname: Cao
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Paul L
authors.initials: PL
authors.lastname: Hermonat
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D011485:Protein Binding; D020079:Terminal Repeat Sequences; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; C093478:E1 protein, Human papillomavirus 16; D009856:Oncogene Proteins, Viral; D014764:Viral Proteins; C068734:rep proteins, Adeno-associated virus 2; D004720:Endonucleases; D000251:Adenosine Triphosphatases; D004265:DNA Helicases