HMG-domain proteins specifically inhibit the repair of the major DNA adduct of the anticancer drug cisplatin by human excision nuclease.

AUTOR(ES)

Huang, J C

RESUMO

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.

Documentos Relacionados

• Selective recognition of a cisplatin-DNA adduct by human mismatch repair proteins.
• The HMG-domain protein BAP111 is important for the function of the BRM chromatin-remodeling complex in vivo
• DNA Damage in the Nucleosome Core Is Refractory to Repair by Human Excision Nuclease
• Differential human nucleotide excision repair of paired and mispaired cisplatin-DNA adducts.
• Recognition and repair of the cyclobutane thymine dimer, a major cause of skin cancers, by the human excision nuclease