Eukaryotic topoisomerase II cleavage of parallel stranded DNA tetraplexes

I. K. Chung, V. B. Mehta, J. R. Spitzner, M. T. Muller

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

A guanine-rich single-stranded DNA from the human immunoglobulin switch region was shown by Sen and Gilbert [Nature, (1988) 334, 364-366] to be able to self-associate to form a stable four-stranded parallel DNA structure. Topoisomerase II did not cleave the single-stranded DNA molecule. Surprisingly, the enzyme did cleave the same DNA sequence when it was annealed into the four-stranded structure. The two cleavage sites observed were the same as those found when this DNA molecule was paired with a complementary molecule to create a normal B-DNA duplex. These cleavages were shown to be protein-linked and reversible by the addition of salt, suggesting a normal topolsomerase II reaction mechanism. In addition, an eight-stranded DNA molecule created by the association of a complementary oligonucleotide with the four-stranded structure was also cleaved by topolsomerase II despite being resistant to restriction endonuclease digestion. These results suggest that a single strand of DNA may possess the sequence Information to direct topoisomerase II to a binding site, but the site must be base paired in a proper manner to do so. This demonstration of the ability of a four-stranded DNA molecule to be a substrate for an enzyme further suggests that these DNA structures may be present in cells.

Original languageEnglish
Pages (from-to)1973-1977
Number of pages5
JournalNucleic acids research
Volume20
Issue number8
DOIs
Publication statusPublished - 1992 Apr 25

Bibliographical note

Funding Information:
We thank D.Sen for helpful discussions, and S.Mirkin and N.Wilkie for critical reading of the manuscript. The work was supported by the National Institutes of Health.

All Science Journal Classification (ASJC) codes

  • Genetics

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