Interaction of bleomycin with a methylated DNA oligonucleotide

Eric C. Long, Sidney Hecht, Gijs A. Van Der Marel, Jacques H. Van Boom

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The extent of DNA cleavage by Fe-bleomycin A2 (Fe-BLM A2) can be diminished substantially in proximity to (5-)methylated cytidine residues. This phenomenon has been attributed to limitations in the ability of certain bleomycin congeners to bind optimally to structurally altered DNA domains, such as those at or adjacent to a site of cytidine methylation, thus reducing reactivity toward bleomycin within those domains. However, diminution of strand scission has been limited to a subset of cleavage sites, generally has not been found to involve the methylated cytidine per se, and has been shown to function only with two BLM congeners. In order to examine the interaction of Fe-BLM A2 with DNA at an isolated site of cytidine methylation at high resolution, and thereby determine whether any change can occur at the actual site of methylation, we have employed the self-complementary DNA oligonucleotide d(CGCTTTAAAGMeCG) as a substrate. Fe·BLM A2 was found to degrade this substrate as effectively as the respective nonmethylated dodecanucleotide, presumably reflecting comparable binding efficiencies for the two oligonucleotides. Two sets of chemical products were obtained when the methylated oligonucleotide was employed as a substrate; these paralleled the products observed when Fe·BLM A2 was used for degradation of the nonmethylated dodecanucleotide d(CGCTTTAAAGCG). However, for the methylated dodecanucleotide, the products included a significantly larger proportion of alkali-labile lesions, as compared with actual strand scission. This finding establishes unequivocally that DNA methylation can affect the chemistry of DNA degradation by BLM even where no diminution of overall degradation occurs. Since both sets of products are believed to derive from a common C-4' deoxyribose radical intermediate, these results suggest that the facility of some subsequent process is altered in the presence of a methylated cytidine moiety.

Original languageEnglish (US)
Pages (from-to)5272-5276
Number of pages5
JournalJournal of the American Chemical Society
Volume112
Issue number13
StatePublished - Jun 20 1990
Externally publishedYes

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Cytidine
Oligonucleotides
Bleomycin
DNA
Methylation
varespladib methyl
Degradation
Substrates
Deoxyribose
DNA Cleavage
Alkalies
DNA Methylation
Complementary DNA

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Long, E. C., Hecht, S., Van Der Marel, G. A., & Van Boom, J. H. (1990). Interaction of bleomycin with a methylated DNA oligonucleotide. Journal of the American Chemical Society, 112(13), 5272-5276.

Interaction of bleomycin with a methylated DNA oligonucleotide. / Long, Eric C.; Hecht, Sidney; Van Der Marel, Gijs A.; Van Boom, Jacques H.

In: Journal of the American Chemical Society, Vol. 112, No. 13, 20.06.1990, p. 5272-5276.

Research output: Contribution to journalArticle

Long, EC, Hecht, S, Van Der Marel, GA & Van Boom, JH 1990, 'Interaction of bleomycin with a methylated DNA oligonucleotide', Journal of the American Chemical Society, vol. 112, no. 13, pp. 5272-5276.
Long EC, Hecht S, Van Der Marel GA, Van Boom JH. Interaction of bleomycin with a methylated DNA oligonucleotide. Journal of the American Chemical Society. 1990 Jun 20;112(13):5272-5276.
Long, Eric C. ; Hecht, Sidney ; Van Der Marel, Gijs A. ; Van Boom, Jacques H. / Interaction of bleomycin with a methylated DNA oligonucleotide. In: Journal of the American Chemical Society. 1990 ; Vol. 112, No. 13. pp. 5272-5276.
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