EFFICIENCY OF DNA-HISTONE CROSS-LINKING INDUCED BY SATURATED AND UNSATURATED ALDEHYDES INVITRO

EFFICIENCY OF DNA-HISTONE CROSS-LINKING INDUCED BY SATURATED AND UNSATURATED ALDEHYDES INVITRO
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DOI:
10.1016/0165-7992(92)90145-8
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发表时间:
1992-10-01
期刊:
MUTATION RESEARCH
影响因子:
--
通讯作者:
BOGDANFFY, MS
BOGDANFFY, MS
中科院分区:
其他
文献类型:
--
作者:
KUYKENDALL, JR;BOGDANFFY, MS

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使用过滤结合试验的基础上沉淀的pUC 13质粒DNA结合小牛胸腺组蛋白,我们已经确定了形成的DNA-蛋白质交联形成的几种醛类化合物在体外诱导的效率。甲醛,戊二醛和丙烯醛是最有效的,导致1交联每2.7 kbp的DNA在1.5,8和150 μ M,分别。所有其它测试的化合物在如下mM浓度范围内每个质粒分子产生1个交联:乙醛,115 mM;丙醛,295 mM;丁醛,360 mM;巴豆醛,8.5 mM;反式-2-戊烯醛,6.3 mM。例如,每分子产生1个交联所需的甲醛浓度几乎比乙醛的浓度低10(5)倍。乙醛与甲醛的区别仅在于一个饱和碳。在2-3个碳之间存在不饱和键提高了交联形成的可能性。例如,丙烯醛的效力比丙醛高500倍以上。戊二醛几乎与甲醛一样有效,表明这种5-碳饱和醛的双官能性质可能对其DNA-蛋白质交联的高效率至关重要。
Using a filter-binding assay based on precipitation of pUC13 plasmid DNA bound to calf-thymus histones, we have determined the efficiency of formation of DNA-protein crosslink formation induced by several aldehyde compounds in vitro. Formaldehyde, glutaraldehyde and acrolein were the most potent, causing 1 crosslink per 2.7 kbp of DNA at 1.5, 8 and 150 muM, respectively. All other compounds tested gave 1 crosslink per plasmid molecule in the mM concentration range as follows: acetaldehyde, 115 mM; propionaldehyde, 295 mM; butyraldehyde, 360 mM; crotonaldehyde, 8.5 mM; trans-2-pentenal, 6.3 mM. Significant decreases in the efficiency of DPXL formation were observed with monofunctional aldehydes of higher carbon chain length. For example, the concentration of formaldehyde needed to give 1 crosslink per molecule was almost 10(5) times less than that of acetaldehyde. Acetaldehyde differs from formaldehyde only by one saturated carbon. The presence of an unsaturated bond between the 2-3 carbons improved the potential for crosslink formation. For example, acrolein was over 500-fold more potent than propionaldehyde. Glutaraldehyde was almost as potent as formaldehyde, indicating that the bifunctional nature of this 5-carbon saturated aldehyde may be crucial to its high efficiency of DNA-protein crosslinking.