Cellular responses against DNA damaged by platinum anticancer drugs

The anticancer activity of platinum-based drugs such as cisplatin, carboplatin, and oxaliplatin is mediated by their ability to attack DNA such that generated adducts trigger numerous cellular responses. A better understanding of these processes is critical for developing more effective therapeutic approaches, which can increase the anti-cancer activity of the drugs while minimizing side effects and extending successful treatment to a wider range of human cancers. Chapter 1 provides the current comprehension of early cellular responses to platinum-DNA adducts. The event primarily occurs through platinum-DNA adduct recognition by a number of cellular proteins. Among proteins that recognize platinum-DNA lesions, one class constitutes proteins that selectively recognize severely distorted DNA generated by the platinum adduct formation. The TATA-binding protein (TBP) and high mobility group protein HMGB1, both highly abundant and vital proteins, are reported to bind cisplatin- damaged DNA and to be involved in mediating the cytotoxic activity of platinum-based agents. Chapters 2 and 3 discuss the structural and kinetic properties of both proteins binding to platinated DNA.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Jung, Yongwon, 1977-

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

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/33746

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/33746