Cisplatin damage overrides the predefined rotational setting of positioned nucleosomes.

Cisplatin damage overrides the predefined rotational setting of positioned nucleosomes. Research Abstract Details 

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Cisplatin damage overrides the predefined rotational setting of positioned nucleosomes. Abstract Text:

Matthias Ober,Stephen J Lippard,

Cisplatin and carboplatin are used successfully to treat various types of cancer. The drugs target the nucleosomes of cancer cells and form intrastrand DNA cross-links that are located in the major groove. We constructed two site-specifically modified nucleosomes containing defined intrastrand cis-{Pt(NH3)2}(2+) 1,3-d(GpTpG) cross-links. Histones from HeLa-S3 cancer cells were transferred onto synthetic DNA duplexes having nucleosome positioning sequences. The structures of these complexes were investigated by hydroxyl radical footprinting. Employing nucleosome positioning sequences allowed us to quantify the structural deviation induced by the cisplatin adduct. Our experiments demonstrate that a platinum cross-link locally overrides the rotational setting predefined in the nucleosome positioning sequence such that the lesion faces toward the histone core. Identical results were obtained for two DNA duplexes in which the sites of platination differed by approximately half a helical turn. Additionally, we determined that cisplatin unwinds nucleosomal DNA globally by approximately 24 degree. The intrastrand cis-{Pt(NH3)2}(2+) 1,3-d(GpTpG) cross-links are located in an area of the nucleosome that contains locally overwound DNA in undamaged reference nucleosomes. Because most nucleosome positions in vivo are defined by the intrinsic DNA sequence, the ability of cisplatin to influence the structure of these positioned nucleosomes may be of physiological relevance.

Cisplatin damage overrides the predefined rotational setting of positioned nucleosomes. Publishing Authors By Initials

M Ober,SJ Lippard,

For similar polynucleotides: oligonucleotides research abstracts see: polynucleotides: oligonucleotides research

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Cisplatin damage overrides the predefined rotational setting of positioned nucleosomes. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of the American Chemical Society

VOLUME: 129

Page Numbers: 6278-86

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 14

MONTH: 04

YEAR: 2007

Cisplatin damage overrides the predefined rotational setting of positioned nucleosomes. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503056

Cisplatin damage overrides the predefined rotational setting of positioned nucleosomes. Keywords Mesh Terms:

KEYWORDS: Oligonucleotides

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Cisplatin damage overrides the predefined rotational setting of positioned nucleosomes. Information

Substance Name: Cisplatin

Registry Number: 15663-27-1

Grant and Affiliation Information for Cisplatin damage overrides the predefined rotational setting of positioned nucleosomes.

AFFILIATION: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA34992

ACRONYM: CA

MEDLINETA: J Am Chem Soc

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