 The induction of E2F by E1A-Rb-HDAC interactions is well documented whereas the consequences of E1A-p300CBP interactions in cell cycle progression are not clear. Previous studies demonstrated that p300CBP prevents premature entry of quiescent cells into S phase by repressing c-Myc transcription through a tripartite repressor complex consisting of p300, YY1, HDAC3. E1A binds to p300 and dissociates the repressor complex to induce S phase. Induction of c-Myc by this mechanism contributes to the induction of DNA damage response and aberrant cellular DNA replication which leads to genomic instability. In a recently published study, it was shown that E1A induces the pivotal DNA replication initiation factor Cdt1 to high levels resulting in increased replication origin activity and in late S phase, induction of DNA damage response and cellular DNA re-replication. Using the single molecule DNA fiber assay, it was discovered that E1A induces significant changes in the dynamics of DNA replication and appears to induce global changes in origin activation. 