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

Authors
  • J C Huang
  • D B Zamble
  • J T Reardon
  • S J Lippard
  • A Sancar
Publication Date
Oct 25, 1994
Source
PMC
Keywords
Disciplines
  • Biology
  • Medicine
License
Unknown

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.

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