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Interaction of mithramycin with DNA fragments complexed with nucleosome core particles: Comparison with Distamycin and Echinomycin

Interaction of mithramycin with DNA fragments complexed with nucleosome core particles: Comparison with Distamycin and Echinomycin
Interaction of mithramycin with DNA fragments complexed with nucleosome core particles: Comparison with Distamycin and Echinomycin

We have studied the sequence-specific interaction of mithramycin with nucleosome core particles which have been reconstituted with various DNA fragments. Mithramycin binds to these DNAs without disrupting the integrity of the nucleosome and produces clear DNase I footprints centered around GC-rich regions. In some instances, the footprints produced on free DNA are resolved into two or more smaller sites when the DNA is complexed with the nucleosome core. In a few cases, novel footprints are produced in sequences which did not bind the drug in free DNA samples. The results are explained by suggesting mithramycin binds to GC-rich regions in which the minor groove faces away from the protein core, and which possess a wider than normal narrow groove on account of their location. Hydroxyl radical footprinting and diethyl pyrocarbonate modification confirm that mithramycin does not affect the rotational positioning of the nucleosome-bound DNA. Although distamycin and echinomycin induce novel DNase I digestion products in nucleosomal DNA which are consistent with the proposed change in DNA positioning [Low, C. M. L., Drew, H. R., & Waring, M. J. (1986) Nucleic Acids Res. 14, 6785–6801], hydroxyl radical footprinting and diethyl pyrocarbonate modification suggest these ligands do not change the rotational positioning of the DNA on the nucleosome cores.

0006-2960
7162-7171
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
Cons, Benjamin M.G.
521b0445-44c9-4f08-872c-959fcf430f88
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
Cons, Benjamin M.G.
521b0445-44c9-4f08-872c-959fcf430f88

Fox, Keith R. and Cons, Benjamin M.G. (1993) Interaction of mithramycin with DNA fragments complexed with nucleosome core particles: Comparison with Distamycin and Echinomycin. Biochemistry, 32 (28), 7162-7171. (doi:10.1021/bi00079a013).

Record type: Article

Abstract

We have studied the sequence-specific interaction of mithramycin with nucleosome core particles which have been reconstituted with various DNA fragments. Mithramycin binds to these DNAs without disrupting the integrity of the nucleosome and produces clear DNase I footprints centered around GC-rich regions. In some instances, the footprints produced on free DNA are resolved into two or more smaller sites when the DNA is complexed with the nucleosome core. In a few cases, novel footprints are produced in sequences which did not bind the drug in free DNA samples. The results are explained by suggesting mithramycin binds to GC-rich regions in which the minor groove faces away from the protein core, and which possess a wider than normal narrow groove on account of their location. Hydroxyl radical footprinting and diethyl pyrocarbonate modification confirm that mithramycin does not affect the rotational positioning of the nucleosome-bound DNA. Although distamycin and echinomycin induce novel DNase I digestion products in nucleosomal DNA which are consistent with the proposed change in DNA positioning [Low, C. M. L., Drew, H. R., & Waring, M. J. (1986) Nucleic Acids Res. 14, 6785–6801], hydroxyl radical footprinting and diethyl pyrocarbonate modification suggest these ligands do not change the rotational positioning of the DNA on the nucleosome cores.

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Published date: 1993

Identifiers

Local EPrints ID: 475664
URI: http://eprints.soton.ac.uk/id/eprint/475664
ISSN: 0006-2960
PURE UUID: fe4d3015-870d-4bc4-90c4-be0af0ed3333
ORCID for Keith R. Fox: ORCID iD orcid.org/0000-0002-2925-7315

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Date deposited: 23 Mar 2023 17:48
Last modified: 17 Mar 2024 02:34

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Contributors

Author: Keith R. Fox ORCID iD
Author: Benjamin M.G. Cons

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