In vivo mapping of DNA topoisomerase II-specific cleavage sites on SV40 chromatin

Liu Yang, Thomas C. Rowe, Eric M. Nelson, Leroy-Fong Liu

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111 Citations (Scopus)

Abstract

The antitumor drug, m-AMSA (4′-(9-acridinylamino)-methanesulfon-m-anisidide), is known to interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II by blocking the enzyme-DNA complex in its putative cleavable state. Treatment of SV40 virus infected monkey cells with m-AMSA resulted in both single- and double-stranded breaks on SV40 viral chromatin. These strand breaks are unusual because they are covalently associated with protein. Immuno-precipitation results suggest that the covalently linked protein is DNA topoisomerase II. These results are consistent with the proposal that the drug action in vivo involves the stabilization of a cleavable complex between topoisomerase II and DNA in chromatin. Mapping of these double-stranded breaks on SV40 viral DNA revealed multiple topoisomerase II cleavage sites. A major topoisomerase II cleavage site was preferentially induced during late infection and was mapped in the DNAase I hypersensitive region of SV40 chromatin.

Original languageEnglish
Pages (from-to)127-132
Number of pages6
JournalCell
Volume41
Issue number1
DOIs
Publication statusPublished - 1985
Externally publishedYes

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ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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