SF2/ASF protein inhibits camptothecin-induced DNA cleavage by human topoisomerase I.
A splicing factor SF2/ASF is a natural substrate for the kinase activity of human topoisomerase I. This study demonstrates that SF2/ASF inhibits DNA cleavage by human topoisomerase I induced by the anti-cancer agent camptothecin. The inhibition is independent of the phosphorylation status of SF2/ASF. We show that the inhibition did not result from binding of SF2/ASF to DNA that would hinder interactions between topoisomerase I and DNA. Neither it was a consequence of a loss of sensitivity of the enzyme to camptothecin. We provide evidence pointing to reduced formation of the cleavable complex in the presence of SF2/ASF as a primary reason for the inhibition. This effect of SF2/ASF is reflected by inhibition of DNA relaxation catalysed by topoisomerase I.
Institute of Biochemistry, Warsaw University, Warsaw, Poland.
Barbara
B
Kowalska-Loth
Agnieszka
A
Girstun
Agnieszka
A
Piekiełko
Krzysztof
K
Staroń
D000972:Antineoplastic Agents, Phytogenic / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002166:Camptothecin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D009690:Nucleic Acid Conformation / Q000187:drug effects; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors
D000972:Antineoplastic Agents, Phytogenic; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D000068103:Serine-Arginine Splicing Factors; D004247:DNA; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin