title: HMG-domain proteins specifically inhibit the repair of the major DNA adduct of the anticancer drug cisplatin by human excision nuclease.
abstract: The most frequent DNA adduct made by the anticancer drug cisplatin, the 1,2-intrastrand d(GpG) cross-link, as well as the minor 1,3-intrastrand d(GpTpG) adduct, were both repaired by an in vitro human excision repair system. Fragments of 27-29 nt containing the platinum damage were excised. The high mobility group (HMG)-domain proteins HMG1 and human mitochondrial transcription factor specifically inhibited repair of the 1,2-intrastrand cross-link by the human excision nuclease. These results suggest that the types and levels of HMG-domain proteins in a given tumor may influence the responsiveness of that cancer to cisplatin chemotherapy and they provide a rational basis for the synthesis of new platinum anticancer drug candidates.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599.
authors.forename: J C
authors.initials: JC
authors.lastname: Huang
authors.forename: D B
authors.initials: DB
authors.lastname: Zamble
authors.forename: J T
authors.initials: JT
authors.lastname: Reardon
authors.forename: S J
authors.initials: SJ
authors.lastname: Lippard
authors.forename: A
authors.initials: A
authors.lastname: Sancar
mesh_terms: D001483:Base Sequence; D002945:Cisplatin / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D006367:HeLa Cells; D006609:High Mobility Group Proteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D013379:Substrate Specificity
chemical_list: D018736:DNA Adducts; D006609:High Mobility Group Proteins; D009838:Oligodeoxyribonucleotides; C057270:cisplatin-DNA adduct; D004706:Endodeoxyribonucleases; D002945:Cisplatin