IXR1, A YEAST PROTEIN THAT BINDS TO PLATINATED DNA AND CONFERS SENSITIVITY TO CISPLATIN
IXR1, A YEAST PROTEIN THAT BINDS TO PLATINATED DNA AND CONFERS SENSITIVITY TO CISPLATIN
复制标题
DOI：
10.1126/science.8342024
复制
发表时间：
1993-07-30
期刊：
影响因子：
56.9
通讯作者：
LIPPARD, SJ
中科院分区：
文献类型：
--
作者：
BROWN, SJ;KELLETT, PJ;LIPPARD, SJ
结构特异性识别蛋白（SSRPs）与含有抗癌药物顺铂形成的链内交联的DNA结合。克隆并测序了编码SSRP的酵母基因，命名为IXR 1。Ixr 1蛋白是高迁移率族蛋白家族的成员，特异性结合顺铂修饰的DNA，但不结合非活性铂化合物。具有失活的IXR 1基因的酵母菌株对顺铂的敏感性为亲本菌株的一半，并且在用顺铂治疗后积累了三分之一的铂-DNA损伤。这些发现表明SSRPs在介导顺铂的细胞毒性中起作用。
Structure-specific recognition proteins (SSRPs) bind to DNA containing intrastrand cross-links formed by the anticancer drug cisplatin. A yeast gene encoding an SSRP, designated IXR1, was cloned and sequenced. The Ixr1 protein, a member of the high mobility group-box protein family, bound specifically to DNA modified with cisplatin but not inactive platinum compounds. A yeast strain with an inactivated IXR1 gene was half as sensitive to cisplatin and accumulated one-third as many platinum-DNA lesions after treatment with cisplatin as the parental strain. These findings suggest that SSRPs play a role in mediating the cytotoxicity of cisplatin.