Selective strand scission by intercalating drugs at DNA bulges

Journal Article · Tue Apr 19 04:00:00 EDT 1988 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00408a051· OSTI ID:7130251

Williams, L D; Goldberg, I H

A bulge is an extra, unpaired nucleotide on one strand of a DNA double helix. This paper describes bulge-specific strand scission by the DNA intercalating/cleaving drugs neocarzinostatin chromophore (NCS-C), bleomycin (BLM), and methidiumpropyl-EDTA (MPE). For this study, the authors have constructed a series of 5'-/sup 32/P end labeled oligonucleotide duplexes that are identical except for the location of a bulge. In each successive duplex of the series, a bulge has been shifted stepwise up (from 5' to 3') one strand of the duplex. Similarly, in each successive duplex of the series, sites of bulge-specific scission and protection were observed to shift in a stepwise manner. The results show that throughout the series of bulged duplexes NCS-C causes specific scission at a site near a bulge, BLM causes specific scission at a site near a bulge, and MPE x Fe(II) causes specific scission centered around the bulge. In some sequences, NCS-C and BLM each cause bulge-specific scission at second sites. Further, bulged DNA shows sites of protection from NCS-C and BLM scission. The results are consistent with a model of bulged DNA with (1) a high-stability intercalation site at the bulge, (2) in some sequences, a second high-stability intercalation site adjacent to the first site, and (3) two sites of relatively unstable intercalation that flank the two stable intercalation sites. On the basis of these results, they propose a new model of the BLM/DNA complex with the site of intercalation on the 3' side (not in the center) of the dinucleotide that determines BLM binding specificity. It appears that specific scission at DNA bulges can be employed as a general assay for intercalation and binding orientation.

• Research Organization: Harvard Medical School, Boston, MA (USA)
• OSTI ID: 7130251
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:8; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

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560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BLEOMYCIN
CARBOXYLIC ACIDS
CHELATING AGENTS
CLATHRATES
COMPLEXES
DAYS LIVING RADIOISOTOPES
DNA
DRUGS
EDTA
ELECTROPHORESIS
GENETIC EFFECTS
ISOTOPES
LIGHT NUCLEI
NEOCARCINOSTATIN
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
OLIGONUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
RADIOISOTOPES
RADIOMIMETIC DRUGS
STRAND BREAKS