Liang Q, Choi D J, Dedon P C
Division of Toxicology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Biochemistry. 1997 Oct 21;36(42):12653-9. doi: 10.1021/bi9718393.
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.
我们研究了药物结构和组蛋白乙酰化在由烯二炔抗生素加利车霉素γII在非洲爪蟾5S rRNA基因上重构的核小体中产生的DNA损伤中的作用。与之前的观察结果一致，与裸露DNA相比，嘌呤序列（-13和-14位）3'-末端的加利车霉素损伤在核小体中增强，而其他位点的损伤在核小体中有所减少。然而，esperamicin C（加利车霉素的类似物，其侧链中缺少末端糖-芳香环）在-13和-14位并未表现出增强作用，并且其在裸露DNA中的序列选择性与加利车霉素明显不同。这突出了完整四糖侧链在识别嘌呤序列3'-末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切割模式。鉴于加利车霉素对局部DNA构象的敏感性，这一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。
