Reaction of anthramycin with DNA. Biological consequences of DNA damage in normal and xeroderma pigmentosum cell lines

R. L. Petrusek, E. L. Uhlenhopp, N. Duteau, L. H. Hurley

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Anthramycin, an antitumor antibiotic produced by Streptomyces refuineus, produces a well defined covalent adduct with DNA and lies within the narrow groove of DNA, attached through a thermal-labile covalent aminal linkage to the exocyclic amino group of guanine, without detectable distortion of the helix. This paper describes results in which the biological consequences of DNA damage and repair by repair-proficient and a repair-deficient xeroderma pigmentosum (XP 12RO) cell line are presented. Anthramycin has been shown to produce excision-dependent single and double strand breaks in DNA, both of which appear to persist many hours after removal of the drug from the media. The lower ability of the xeroderma pigmentosum cell line to remove anthramycin lesions from DNA is correlated with a decreased cell survival. The biological consequences of DNA damage (genetic effects, DNA strand breakage, and cytotoxicity) are discussed with respect to the defined structure and stability of the anthramycin-deoxyguanosine adduct.

Original languageEnglish (US)
Pages (from-to)6207-6216
Number of pages10
JournalJournal of Biological Chemistry
Volume257
Issue number11
StatePublished - Dec 1 1982
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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