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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
51
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pubmed:dateCreated |
1996-2-1
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pubmed:abstractText |
The specific cleavage of a DNA triple helix by FeII.bleomycin (BLM) is demonstrated. Triplex-specific cleavage was observed on both strands of the 32-base pair (bp) duplex at the duplex-triplex junctions. Strand scission products and alkali labile lesions were both formed. The strongest BLM cleavage site was located at the 5'-duplex-triplex junction, which is also the preferred triplex binding site of intercalating agents [Collier, D. A., Mergny, J.-L., Thuong, N. T., & Hélène, C. (1991) Nucleic Acids Res. 19, 4219-4224]. The preference of BLM for the 5'-junction does not appear to derive from selective intercalative binding at this site. This is supported by the observation that phleomycin, which contains a thiazolinylthiazole moiety rather than a planar bithiazole ring system, exhibited the same selectivity of triplex cleavage as BLM. Cleavage of the triple helix by FeII.BLM was unaffected by concentrations of Mg2+ up to 5 mM, suggesting possible therapeutic applications of this novel DNA target. Molecular-modeling calculations of the triplex region suggested that dramatic variations in minor groove width and depth occur at the duplex-triplex junctions, particularly at the 5'-junction. Moreover, the minor groove at these sites was calculated to be somewhat shallower and wider than the minor groove of B-DNA. These results suggest that the preference of BLM for the duplex-triplex junctions derives from selective recognition of minor groove shape at these sites and thus reflects conformation-selective, rather than sequence-selective, DNA recognition by FeII.BLM.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Bleomycin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Phleomycins,
http://linkedlifedata.com/resource/pubmed/chemical/iron bleomycin
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
34
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
16715-24
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8527446-Antibiotics, Antineoplastic,
pubmed-meshheading:8527446-Base Sequence,
pubmed-meshheading:8527446-Binding Sites,
pubmed-meshheading:8527446-Bleomycin,
pubmed-meshheading:8527446-DNA,
pubmed-meshheading:8527446-Molecular Sequence Data,
pubmed-meshheading:8527446-Molecular Structure,
pubmed-meshheading:8527446-Nucleic Acid Conformation,
pubmed-meshheading:8527446-Oligodeoxyribonucleotides,
pubmed-meshheading:8527446-Phleomycins
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pubmed:year |
1995
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pubmed:articleTitle |
Specific cleavage of a DNA triple helix by FeII.bleomycin.
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pubmed:affiliation |
Department of Chemistry, University of Virginia, Charlottesville 22901, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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