HMG-DOMAIN PROTEINS SPECIFICALLY INHIBIT THE REPAIR OF THE MAJOR DNA ADDUCT OF THE ANTICANCER DRUG CISPLATIN BY HUMAN EXCISION NUCLEASE
HMG-DOMAIN PROTEINS SPECIFICALLY INHIBIT THE REPAIR OF THE MAJOR DNA ADDUCT OF THE ANTICANCER DRUG CISPLATIN BY HUMAN EXCISION NUCLEASE
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DOI：
10.1073/pnas.91.22.10394
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发表时间：
1994-10-25
影响因子：
11.1
通讯作者：
SANCAR, A
中科院分区：
文献类型：
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作者：
HUANG, JC;ZAMBLE, DB;SANCAR, A
最常见的DNA加合物由抗癌药物顺铂，1，2-intrastrand d（GpG）交联，以及次要的1，3-intrastrand d（GpTpG）加合物，都修复了体外人类切除修复系统。切除含有铂损伤的27-29 nt的片段。高迁移率族（HMG）结构域蛋白HMG 1和人线粒体转录因子特异性抑制修复的1，2-链内交联的人切除核酸酶。这些结果表明，在一个给定的肿瘤HMG结构域蛋白的类型和水平可能会影响该癌症的顺铂化疗的反应性，他们提供了一个合理的基础上，新的铂类抗癌药物的候选人的合成。
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.