 The Myst family protein HBO1 Myst2, KAT7 is a histone acetyl transferase that plays a major role in replication initiation and also contributes to DNA re-replication. HBO1 directly interacts with Cdt1 and functions as a coactivator of Cdt1 in replication initiation. It also associates with replication origin and stimulates origin activation by acetylating H4 K5, K8, and K12. Overexpression of HBO1 induces DNA re-replication. The enrichment of chromatin modifications including acetylation of H4 histones at the origins strongly influences origin activation. Thus, E1A in the absence of a multitude of serum stimulated proliferation signals, forces cells to enter S phase using several compensatory mechanisms. Uncontrolled cellular DNA replication program causes polyploidy that is the hallmark of cancer. It is exciting that a viral oncogene such as E1A alters the cellular DNA replication program. This raises a number of important questions related to the mechanism of replication stress induced by a viral oncogene. For example, how does E1A induce DNA re-replication? Does E1A stimulation of HBO1 alter initiation mechanism and whether HBO1 mediated chromatin modifications at the origins promote re-replication? 