title: Evidence for DNA charge transport in the nucleus.
abstract: Oxidative damage to DNA bases in isolated HeLa nuclei occurs upon treatment with rhodium intercalators and photoactivation. Oxidation occurs preferentially at the 5'-guanine of 5'-GG-3' sites, indicative of base damage by DNA-mediated charge transfer chemistry. Moreover, oxidative damage occurs at protein-bound sites which are inaccessible to rhodium. Thus, on transcriptionally active DNA within the cell nucleus, DNA-mediated charge transport leads to base damage from a distance, and direct interaction of an oxidant is not necessary to generate a base lesion at a specific site. These observations require consideration in designing new chemotherapeutics and in understanding cellular mechanisms for DNA damage and repair.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Núñez
authors.forename: G P
authors.initials: GP
authors.lastname: Holmquist
authors.forename: J K
authors.initials: JK
authors.lastname: Barton
mesh_terms: D001483:Base Sequence; D002467:Cell Nucleus / Q000737:chemistry* / Q000235:genetics; D019744:Chemokines, C; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D004249:DNA Damage; D004579:Electron Transport / Q000235:genetics; D016158:Genes, p53; D006147:Guanine / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry; D008222:Lymphokines; D008969:Molecular Sequence Data; D009942:Organometallic Compounds / Q000737:chemistry; D018384:Oxidative Stress / Q000235:genetics; D011401:Promoter Regions, Genetic; D012795:Sialoglycoproteins; D014158:Transcription, Genetic
chemical_list: D019744:Chemokines, C; D007364:Intercalating Agents; D008222:Lymphokines; D009942:Organometallic Compounds; D012795:Sialoglycoproteins; C092390:XCL1 protein, human; C104747:bis(phenanthrenequinonediimine)(4,4'-dimethyl-2,2'-dipyridine)rhodium(III); C018997:lymphotactin; D006147:Guanine; D004247:DNA