 the investigators will first determine whether E1A directly binds to HBO1 by performing the GST binding and in vivo co-IP experiments. If binding is confirmed, the investigators will map the binding sites on both proteins. the investigators will then isolate mutants of both proteins that abolish the interactions. All E1A mutants will be evaluated for their interactions with Rb and p300 and only mutants that retain their capacity to bind to these proteins will be used. It will be necessary to isolate an HBO1 mutant that retains E1A binding capacity but lacks the HAT activity. A widely used HAT deficient mutant G435A will be used in these studies. If E1A binds to this mutant, it will be a valuable mutant to confirm that E1A induced HAT activity is critical for stimulation of replication initiation. If this HBO1 mutant does not bind to E1A, it will be important to isolate new HBO1 mutants which retain E1A binding capacity but lack HAT activity. 