HMG-DOMAIN PROTEINS SPECIFICALLY INHIBIT THE REPAIR OF THE MAJOR DNA ADDUCT OF THE ANTICANCER DRUG CISPLATIN BY HUMAN EXCISION NUCLEASE

被引：331
作者：
HUANG, JC [1 ]
ZAMBLE, DB [1 ]
REARDON, JT [1 ]
LIPPARD, SJ [1 ]
SANCAR, A [1 ]
机构：
[1] MIT, DEPT CHEM, CAMBRIDGE, MA 02139 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1994年 / 91卷 / 22期
关键词：
CHEMOTHERAPY; DNA REPAIR; XERODERMA PIGMENTOSUM;
D O I：
10.1073/pnas.91.22.10394
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
The most frequent DNA adduct made by the anticancer drug cisplatin, the 1,2-intrastrand d(GpG) crosslink, 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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页码：10394 / 10398
页数：5
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