CHED 108

Cisplatin interstrand cross-linking of defined sequence nucleosomal DNA

Erin E. Wilkes and Julie T. Millard. Department of Chemistry, Colby College, 5757 Mayflower Hill, Waterville, ME 04901, fax: 207-872-3804, eewilkes@colby.edu

DNA interstrand cross-linking agents have been recognized for many years to be powerful antitumor chemotherapeutics. While the interactions between free DNA and many anticancer drugs have been explored extensively, there is less information available about these interactions with nucleosomal DNA. Nitrogen mustards have been reported to show relatively similar cross-linking sites and efficiencies in free and nucleosomal DNA, but mitomycin C shows markedly reduced cross-linking in the center of nucleosomal DNA. We have initiated studies on the cisplatin-induced interstrand cross-linking of the 5S DNA of Xenopus borealis reconstituted with chicken histones to form defined sequence nucleosome core particles. We are using polyacrylamide gel electrophoresis to examine the families of cross-links produced in the free and nucleosomal state.