Calicheamin-mediated DNA damage in a reconstituted nucleosome is not affected by histone acetylation: the role of drug structure in the target recognition process.
Calicheamin-mediated DNA damage in a reconstituted nucleosome is not affected by histone acetylation: the role of drug structure in the target recognition process.
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DOI：
10.1021/bi9718393
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发表时间：
1997-10
期刊：
影响因子：
2.9
通讯作者：
Q. Liang;D. J. Choi;P. Dedon
中科院分区：
文献类型：
--
作者：
Q. Liang;D. J. Choi;P. Dedon
我们已经研究了药物结构和组蛋白乙酰化在DNA损伤中的作用，所产生的烯二炔类抗生素加利车霉素gammaII在核小体上重建的5S rRNA基因的爪蟾borealis。与先前的观察结果一致，与裸DNA相比，核小体中嘌呤段3 '端（位置-13和-14）的卡奇霉素损伤增强，而核小体中其他位点的损伤有所减少。然而，由esperamicin C（一种在侧链中缺失末端糖芳香环的加利车霉素类似物）产生的损伤在位置-13和-14处没有显示出增强，并且其在裸DNA中的序列选择性与加利车霉素的序列选择性显著不同。这突出了完整的四糖侧链在识别嘌呤束3 '端发生的结构变形中的重要性。两种药物在正常和高乙酰化核小体中产生相同的裂解模式。鉴于加利车霉素对局部DNA构象的敏感性，该观察结果与其他研究一致，这些研究表明单独的组蛋白乙酰化不会显著影响核小体中核心DNA的局部构象。
We have examined the role of drug structure and histone acetylation in DNA damage produced by the enediyne antibiotic calicheamicin gammaII in nucleosomes reconstituted onto the 5S rRNA gene of Xenopus borealis. Consistent with previous observations, calicheamicin damage at the 3'-end of a purine tract (positions -13 and -14) was enhanced in the nucleosome compared to the naked DNA while damage at other sites was somewhat reduced in the nucleosome. However, damage produced by esperamicin C, an analog of calicheamicin missing the terminal sugar-aromatic ring in the side chain, showed no enhancement at positions -13 and -14, and its sequence selectivity in naked DNA was markedly different from that of calicheamicin. This highlights the importance of the intact tetrasaccharide side chain in the recognition of the structural deformation occurring at the 3'-ends of purine tracts. Both drugs produced identical cleavage patterns in normal and hyperacetylated nucleosomes. Given the sensitivity of calicheamicin to local DNA conformation, this observation is consistent with other studies that suggest that histone acetylation alone does not significantly affect the local conformation of core DNA in the nucleosome.