The modulation of topoisomerase I-mediated DNA cleavage and the induction of DNA-topoisomerase I crosslinks by crotonaldehyde-derived DNA adducts.
The modulation of topoisomerase I-mediated DNA cleavage and the induction of DNA-topoisomerase I crosslinks by crotonaldehyde-derived DNA adducts.
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DOI：
10.1093/nar/gkn334
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发表时间：
2008-07
影响因子：
14.9
通讯作者：
Pommier Y
中科院分区：
文献类型：
--
作者：
Dexheimer TS;Kozekova A;Rizzo CJ;Stone MP;Pommier Y
巴豆醛是一种代表性的 α,β-不饱和醛，具有与 DNA 反应倾向相关的致突变和致癌特性。环状巴豆醛衍生的脱氧鸟苷 (CrA-PdG) 加合物可以在双链 DNA 中进行开环，产生高反应性的醛部分。在这里，我们证明含有单个 CrA-PdG 加合物的位点特异性修饰的 DNA 寡核苷酸可以直接或间接与拓扑异构酶 I (Top1) 形成交联。用氰基硼氢化钠还原后，可检测到 CrA-PdG 加合物和 Top1 之间直接形成共价复合物，这与 Top1 和加合物的开环醛形式之间形成希夫碱一致。此外，我们还发现 CrA-PdG 加合物改变了 Top1 的裂解和再连接活性。它抑制加合物位点的 Top1 裂解复合物，并在 CrA-PdG 加合物附近诱导可逆和不可逆裂解复合物。稳定的 DNA-Top1 交联的形成和 CrA-PdG 诱导 Top1 裂解复合物是相互排斥的。最后，我们发现巴豆醛诱导哺乳动物细胞中 DNA-Top1 复合物的形成，这表明 DNA-Top1 交联的形成与巴豆醛的诱变和致癌特性之间存在潜在关系。
Crotonaldehyde is a representative α,β-unsaturated aldehyde endowed of mutagenic and carcinogenic properties related to its propensity to react with DNA. Cyclic crotonaldehyde-derived deoxyguanosine (CrA-PdG) adducts can undergo ring opening in duplex DNA to yield a highly reactive aldehydic moiety. Here, we demonstrate that site-specifically modified DNA oligonucleotides containing a single CrA-PdG adduct can form crosslinks with topoisomerase I (Top1), both directly and indirectly. Direct covalent complex formation between the CrA-PdG adduct and Top1 is detectable after reduction with sodium cyanoborohydride, which is consistent with the formation of a Schiff base between Top1 and the ring open aldehyde form of the adduct. In addition, we show that the CrA-PdG adduct alters the cleavage and religation activities of Top1. It suppresses Top1 cleavage complexes at the adduct site and induces both reversible and irreversible cleavage complexes adjacent to the CrA-PdG adduct. The formation of stable DNA–Top1 crosslinks and the induction of Top1 cleavage complexes by CrA-PdG are mutually exclusive. Lastly, we found that crotonaldehyde induces the formation of DNA–Top1 complexes in mammalian cells, which suggests a potential relationship between formation of DNA–Top1 crosslinks and the mutagenic and carcinogenic properties of crotonaldehyde.
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影响因子：
14.9
作者：
Antony, S;Theruvathu, JA;Pommier, Y
通讯作者：
Pommier, Y
DOI：
10.1016/s0027-5107(99)00009-3
发表时间：
1999-03-08
影响因子：
2.3
作者：
Chung, FL;Nath, RG;Randerath, K
通讯作者：
Randerath, K
DOI：
10.1016/0165-7992(92)90145-8
发表时间：
1992-10-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
KUYKENDALL, JR;BOGDANFFY, MS
通讯作者：
BOGDANFFY, MS
影响因子：
2.8
作者：
Fernandes, PH;Kanuri, M;Lloyd, RS
通讯作者：
Lloyd, RS
影响因子：
2.9
作者：
Cho, Young-Jin;Kozekov, Ivan D.;Stone, Michael P.
通讯作者：
Stone, Michael P.