Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents, Phytogenic / antagonists & inhibitors*
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Antineoplastic Agents, Phytogenic / pharmacology
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Camptothecin / antagonists & inhibitors*
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Camptothecin / pharmacology
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DNA / metabolism*
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DNA Damage
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DNA Topoisomerases, Type I / metabolism*
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Electrophoretic Mobility Shift Assay
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Humans
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Nuclear Proteins / chemistry
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Nuclear Proteins / pharmacology
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Nuclear Proteins / physiology*
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Nucleic Acid Conformation / drug effects
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Phosphorylation
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Protein Processing, Post-Translational
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RNA-Binding Proteins
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Recombinant Fusion Proteins / metabolism
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Serine-Arginine Splicing Factors
Substances
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Antineoplastic Agents, Phytogenic
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Nuclear Proteins
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RNA-Binding Proteins
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Recombinant Fusion Proteins
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Serine-Arginine Splicing Factors
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DNA
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DNA Topoisomerases, Type I
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Camptothecin