How Do Drug-Induced Topoisomerase I-DNA Lesions Signal to the Molecular Interaction Network that Regulates Cell Cycle Checkpoints, DNA Replication, and DNA Repair?

Recent results suggest that potentially lethal DNA lesions may result when replication forks encounter trapped topoisomerase-DNA complexes or some other types of DNA damage. Such events produce what are called replication-encounter lesions. These lesions have the characteristic that they may allow single stranded DNA-associated replication protein A (RPA) to become juxtaposed to dsDNA end-associated DNA-protein kinase. Our results suggest that...