Figure 1. Etoposide-induced DNA breaks detected by CFGE.

A homodimer of topoII binds and cleaves cellular DNA. Etoposide binds independently to each monomer to block religation and thereby locks the topoII-DNA complex. At low concentrations, only one of the topoII monomers will be bound by etoposide and unable to religate the break, resulting in a topoII-linked SSB (a). When both monomers are occupied by etoposide, a topoII-linked DSB will be generated (b). In CFGE cells are lysed and proteins removed from DNA by SDS and proteinase K, allowing detection of protein-linked SSBs and DSBs.