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

被引：330

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.

引用

页码：10394 / 10398

页数：5

共 28 条

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