Figure 6.

Proposed model for E1 and E2 function in viral replication and maintenance in the cell cycle. Hypophosphorylated E2 loads E1 monomers onto DNA in G₁ phase, facilitating E1 multimerization into the active double hexameric E1 helicase and release of E2 from DNA in S phase. After replication, E1 and E2 bind to viral DNA and E2 can be phosphorylated by a G₂/M kinase facilitating chromosomal binding. The DNA can then be accurately partitioned to daughter cells and retained in nuclear structures reformed around the cellular chromosomes in telophase. The oligomeric state of E1 and E2 as attached to the chromosome is hypothetical and based on the findings that show a 1:1 complex between an E2 dimer and an E1 monomer. Suppressor mutations in E1 may arise that do not require E2 phosphorylation because these new E1 proteins create a stronger binding surface for either E2 or the chromosome. To start the cycle anew, E2 can be synthesized de novo or a phosphate can be removed from E2. The E2 and E1 functions in regulating transcription are not included here.