Evidence for DNA charge transport in the nucleus.
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.
Núñez
M E
ME
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Holmquist
G P
GP
Barton
J K
JK
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
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