ANALYSIS OF C-MYC DOMAINS INVOLVED IN STIMULATING SV40 REPLICATION

We have demonstrated previously that overproduction of c-Myc, N-Myc an d, to a lesser extent, L-Myc facilitates the replication of simian vir us 40 (SV40)-based vectors in human lymphoid cells. Using a series of c-myc deletion mutants, we investigated which c-Myc regions are import ant in stimulating SV40 replication. The ability of c-Myc to promote S V40 replication was significantly reduced by deletions in the second e xon domain, formerly shown to be crucial for c-Myc's transforming capa city. The c-myc mutants with a disrupted basic region (b) or leucine z ipper (Zip) motif were also unable to stimulate SV40 replication. Thes e regions are implicated in protein-DNA and protein-protein interactio ns, respectively, suggesting that the c-Myc protein might be associate d with the DNA-protein replication complex. We present data obtained f rom gel mobility shift assays and from an immunocomplex-binding assay substantiating this hypothesis.