Document 1075
 DOCN  M9471075
 TI    Alternative dna structures in topoisomerase II-DNA interactions.
 DT    9409
 AU    Howard MT; Univ. of North Carolina at Chapel Hill
 SO    Diss Abstr Int [B]; 53(9):4481 1993. Unique Identifier : AIDSLINE
       ICDB/94690788
 AB    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.)
 DE    Animal  Binding Sites  DNA/CHEMISTRY/*METABOLISM  DNA Topoisomerase
       (ATP-Hydrolysing)/*METABOLISM  Drosophila  Escherichia coli/ENZYMOLOGY
       Nucleic Acid Conformation  THESIS

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