Sequence specificity of DNA-DNA interstrand cross-link formation by cisplatin and dinuclear platinum complexes.
Sequence specificity of DNA-DNA interstrand cross-link formation by cisplatin and dinuclear platinum complexes.
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顺铂和双核铂络合物形成 DNA-DNA 链间交联的序列特异性。
DOI：
10.1021/bi00184a007
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发表时间：
1994
期刊：
影响因子：
2.9
通讯作者：
Farrell,N
中科院分区：
文献类型：
--
作者：
Zou,Y;VanHouten,B;Farrell,N
摘要：在49个碱基对的DNA双链体中，单核和双核铂络合物在DNA中诱导的链间交联的序列特异性已被直接测定。这种新的测定利用了随机铂化DNA的3 '-*·5'外切核酸酶消化产生不同长度的片段库的事实。这种处理允许鉴定阻碍核酸外切酶切割的加合物的谱。链间交联加合物产生的片段在结合位点附近可以保持互补。因此，这些片段可以作为引物模板，在随后用DNA聚合酶处理时进行延伸。这种延伸增加了寡核苷酸片段的大小，这可以通过测序凝胶上更缓慢迁移的条带来证明。同时，对应于消化的交联的原始条带的强度降低。因此，比较仅消化后的测序凝胶和“消化-延伸”处理后的测序凝胶应显示仅具有链间交联的那些片段的消失或条带强度的减弱。将该方法应用于由cij-[PtCl 2（NH 3）2]（cij-DDP）和[{trnj-PtCl（NH 3）2} 2 H2 N（CH 2）4 NH 2] Cl 2形成的DNA链间交联的分析。cij-DDP被证实在d（GC）序列处形成链间交联，但有趣的是，链间交联在序列GCGG中占主导地位，可能形成1，3-链内交联，但不形成1，2-链内交联。该双核化合物在相对链上的鸟嘌呤之间形成1，2，1，3和1，4 DNA链间交联。在1，3和1，4交联中，鸟嘌呤分别被一个和两个碱基对分开，而1，2交联由相邻碱基对上的鸟嘌呤形成。许多临床上重要的药物的细胞毒性和抗癌活性被认为是通过DNA-DNA链间交联的形成而与DNA反应的结果（Kohn，1983; Roberts，1987; Robertsetal.，1988年; Tomaszetal.，1987年）。链间交联剂也存在作为结构探针的可能应用（Wavel等人，1992; Cimino等人，1985）和反义寡核苷酸的开发（Gruff & Orgel，1991; Chu & Orgel，1990; Uhlmann &
Revised Manuscript Received March 11, 1994® abstract: The sequence specificity of interstrand cross-links induced in DNA by mononuclear and dinuclear platinum complexes in a 49-base-pair DNA duplex has been determined directly. This new assay takes advantage of the fact that 3'—*•5'exonuclease digestion of randomly platinated DNA produces a pool of fragments of different lengths. This treatment allows identification of the spectrum of adducts impeding the exonuclease scission. Interstrand cross-linked adducts produce fragments that may remain complementary in the proximityof the binding site. As a result, these fragments may act as primer templates for extension upon subsequent treatment with a DNA polymerase. This extension increases the size of the oligonucleotide fragments, which may be evidencedby a more slowly migrating band on a sequencing gel. Concomitantly, the original band corresponding to the digested cross-link decreases in intensity. Therefore, comparison of a sequencing gel after digestion only and after the “digestion-extension” treatment should show the disappearance, or diminished band intensity, of only those fragmentswith interstrand cross-links. This approach was applied to the analysis of DNA interstrand cross-links formed by cij-[PtCl2 (NH3) 2](cij-DDP) and [{tr «nj-PtCl (NH3) 2} 2H2N (CH2) 4NH2] Cl2. cij-DDP was confirmed to form interstrand cross-links at d (GC) sequences but, interestingly, interstrand cross-links predominated in a sequence GCGG, with possible 1, 3-intrastrand but no 1, 2-intrastrand cross-links forming. The dinuclear compound formed 1, 2, 1, 3, and 1, 4 DNA interstrand cross-linksbetween guanines on opposite strands. In 1, 3 and 1, 4 cross-links, the guanines are separated by one and two base pairs, respectively, whereas a 1, 2 cross-link is formed from guanines on neighboring base pairs. The applicability of the approach was extended by examining the interstrand cross-links formed by 4'-(hydroxymethyl) d (TA) sequence specificity was observed.The cytotoxicity and anticancer activityof many clinically important drugs are believed to result from reaction with DNA by the formation of DNA-DNA interstrand cross-links (Kohn, 1983; Roberts, 1987; Robertsetal., 1988; Tomaszetal., 1987). Interstrand cross-linking agents also present possible applications as structural probes (Alul et al., 1992; Cimino et al., 1985) and in the development of antisense oligonucleotides (Gruff & Orgel, 1991; Chu & Orgel, 1990; Uhlmann &
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影响因子：
11.2
作者：
J. Gralla;S. Sasse-Dwight;L. Poljak
通讯作者：
J. Gralla;S. Sasse-Dwight;L. Poljak
构建在独特位点用补骨脂素修饰的 DNA 底物，并研究 ABC 核酸外切酶对这些均匀修饰的底物的作用机制。
DOI：
--
发表时间：
1986
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
VanHouten,B;Gamper,H;Hearst,JE;Sancar,A
通讯作者：
Sancar,A
影响因子：
2.1
作者：
HOPKINS, PB;MILLARD, JT;RAUCHER, S
通讯作者：
RAUCHER, S
顺式二氯二氨铂 (II) 与培养细胞或体外 DNA 反应后 DNA 中链间交联的频率：DNA 交联的稳定性及其修复。
影响因子：
5.1
作者：
J. Roberts;F. Friedlos
通讯作者：
F. Friedlos
优化 PtII 寡核苷酸硫代磷酸酯复合物与互补寡核苷酸的交联效率。
影响因子：
14.9
作者：
Chu,BC;Orgel,LE
通讯作者：
Orgel,LE