Cisplatin-induced nucleosome and RNA polymerase II modification mediate cellular response to the drug

(cont.) with recombinant material. The in vitro system established in this study will facilitate the investigation of platinum-DNA damage by DNA repair processes and help elucidate the role of specific post-translational modification in NER of platinum-DNA adducts at the physiologically relevant nucleosome level. Chapter 3: Nucleotide Excision Repair of Site-Specifically Platinum-Modified Tetrasomes. The nucleosome, the basic structural unit of chromatin, is composed of a histone (H3/H4)₂ tetramer flanked by two H2A/H2B dimers, around which is wrapped 146 base pairs (bp) of DNA. The (H3/H4)₂ tetramer plays a central role in the structural integrity and positioning of the nucleosome core particle. Site- specifically platinated tetrasomes were prepared to investigate the modulating effects of histone tetramers on excision repair of cisplatin-intrastrand cross-links. In addition, (Pt(DACH))²⁺-modified tetrasome was prepared to investigate the effect of spectator ligands on excision repair of platinated tetrasomes. The NER results reveal that the (H3/H4)₂ tetramer is sufficient to block excision of both cisplatin-DNA and Pt(DACH))²⁺-DNA adduct in vitro. The efficiency of excision of cisplatin-modified tetrasomal DNA is about half (53%) that of the [Pt(DACH)]²⁺-modified tetrasome. Chapter 4: Cisplatin Adducts Change the Rotational Positioning of DNA on the Nucleosome ...

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2004

Author dc:creator

• Wang, Dong, 1975-

Advisor dc:contributor.advisor

• Stephen J. Lippard.

• Chemistry.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/28693

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/28693