Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Alternative dna structures in topoisomerase II-DNA interactions.
Diss Abstr Int [B]; 53(9):4481 1993. Unique Identifier : AIDSLINE ICDB/94690788 Howard MT; Univ. of North Carolina at Chapel Hill
Abstract:
The type II DNA topoisomerases are enzymes that can change the topological state of DNA. This is accomplished by passing DNA strands through each other via a transient break in the helix. The result of this reaction is to relax or introduce DNA supercoils and to resolve knotted or catenated DNAs. Topoisomerase activity is essential for many aspects of DNA metabolism such as transcription which generates waves of DNA supercoiling and replication that produces catenated daughter DNAs. Several compounds that inhibit topoisomerase II are highly toxic to actively replicating cells and have been used as anti-tumor agents. These inhibitors act by trapping a topoisomerase II-DNA complex at the cleavage step of the catalytic cycle. DNA cleavage can be captured by exposing the complexes to a protein denaturants such as SDS. Analysis of the cleavage products reveals that topoisomerase II acts at specific locations on the DNA with some sequence preferences. In this study we report that alternative DNA structures can affect topoisomerase II-DNA interactions. A strong binding site for Drosophila topoisomerase II was created by a sequence directed DNA bend. The shape of the bend brings two distant DNA segments into close proximity creating a DNA crossover or node. Because topoisomerase II binds two DNA segments simultaneously it preferentially localizes to this structure. In the absence of a fixed DNA crossover, topoisomerase II captures two DNA segments by random collision. DNA gyrase, the type II topoisomerase from E coli, did not recognize this structure although it did bind two DNA segments simultaneously via a random collision event. We have identified a cluster of strong topoisomerase II sites which map to a complex repeated sequence element flanking the HIV isolate HXB2. This region is capable of forming slipped pairing structures, cruciforms, or Z-DNA. We conclude that topoisomerase II-DNA interactions can be affected by DNA structure in addition to the primary sequence of DNA. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD93-02534.)
Keywords: Animal Binding Sites Drosophila DNA/CHEMISTRY/*METABOLISM DNA Topoisomerase (ATP-Hydrolysing)/*METABOLISM Escherichia coli/ENZYMOLOGY Nucleic Acid Conformation THESIS
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Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
