Open AccessHMG-domain proteins specifically inhibit the repair of the major DNA adduct of the anticancer drug cisplatin by human excision nuclease.
Author(s) -
Juch Chin Huang,
Deborah B. Zamble,
Joyce T. Reardon,
Stephen J. Lippard,
Aziz Sancar
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.22.10394
Subject(s) - cisplatin , nuclease , nucleotide excision repair , dna repair , dna , adduct , dna damage , chemistry , carboplatin , biology , biochemistry , chemotherapy , genetics , organic chemistry
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.