Gene expression rather than the initiation of DNA replication is the principal target of lethal u.v.-induced damage in a regulatory region of SV40 DNA

The survival of transfected simian virus (SV) 40 DNA is acutely sensitive to damage in a 302-bp regulatory region that governs viral gene expression and the initiation of viral DNA replication. We investigated whether the lethal effect of damage in this region is due to the disruption of gene expression or to the inhibition of DNA replication by comparing the survival of damaged viral DNA in CV-1 and cos-1 African green monkey cells. Viral early sequences integrated into the genomic DNA of cos-1 cells complement the growth of virus with defective early genes and were therefore expected to reverse viral sensitivity to lesions that interfere with early gene expression. Our results indicate that viral sensitivity to damage in the regulatory region is almost completely abolished in cos-1 cells. This finding identifies gene expression rather than the initiation of DNA replication as the major target for lethal damage in the portion of the SV40 genome. Sensitivity to damage in the viral late gene region is the same in CV-1 and cos-1 cells, indicating that cos-1 cells are not merely more proficient in host-cell reactivation. (author)