Please do not disturb: destruction of chromatin structure by supravital nucleic acid probes revealed by a novel assay of DNA-histone interaction.
Please do not disturb: destruction of chromatin structure by supravital nucleic acid probes revealed by a novel assay of DNA-histone interaction.
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DOI：
10.1002/cyto.a.20622
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发表时间：
2008-10
期刊：
影响因子：
3.7
通讯作者：
Darzynkiewicz, Zbigniew
中科院分区：
文献类型：
--
作者：
Wlodkowic, Donald;Darzynkiewicz, Zbigniew
被设计用于超临界状态的生物标志物对细胞的结构和功能的影响预计将微乎其微。不幸的是，几乎所有开发来探测活细胞的荧光染料都以不受欢迎的方式与细胞成分相互作用，并影响功能途径。鉴于Wojcik和Dobrucki最近在DRAQ 5和Syto 17上发表的文章，我们评论了各种DNA结合探针的潜在应用。这些作者使用带有荧光蛋白标记的组蛋白的细胞来评估DNA-组蛋白相互作用的方法，为研究针对DNA的抗肿瘤药物的作用机制提供了一个有价值的工具。虽然许多插层药物的效果可能与DRAQ5相似，但观察链内和链间DNA交联剂、烷化剂、组蛋白去乙酰酶抑制剂甚至抗代谢物的效果可能特别有趣。因此，具有荧光蛋白标记的组蛋白的细胞可以作为生物标记物来探索针对DNA或影响染色质结构的药物的作用机制。事实上，由于组蛋白从DNA中解离和分离所揭示的染色质粗大变化很可能与细胞的长期存活不相容，因此该方法可用于研究中的抗肿瘤药物的快速筛选。
The biomarkers designed to be used supravitally are expected to have minimal effect on structure and function of the cell. Unfortunately nearly all fluorochromes developed to probe live cells interact in undesired way with cellular constituents and affect functional pathways. Herein we comment on potential applications of diverse DNA binding probes in view of the recent article by Wojcik & Dobrucki on DRAQ 5 and SYTO 17. The approach used by these authors to assess DNA-histone interactions using the cells having histones tagged with fluorescent proteins offers a valuable tool to study mechanism of action of antitumor drugs targeting DNA. While the effect of many intercalating drugs may be similar to that of DRAQ5, it may be of particular interest to observe the effects induced by intra-strand and inter-strand DNA crosslinking drugs, alkylating agents, histone deacetylase inhibitors or even anti-metabolites. The cells having histones tagged with fluorescent proteins thus may serve as biomarkers to probe mechanism of action of drugs targeting DNA or affecting chromatin structure. In fact, because such gross chromatin changes as revealed by dissociation and segregation of histones from DNA are most likely incompatible with long-term cell survival, the methodology may be applied for rapid screening of investigational antitumor agents.
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影响因子：
3.7
作者：
Halicka, HD;Bedner, E;Darzynkiewicz, Z
通讯作者：
Darzynkiewicz, Z
DOI：
10.1073/pnas.86.13.5151
发表时间：
1989-07-01
影响因子：
11.1
作者：
BARTKOWIAK, J;KAPUSCINSKI, J;DARZYNKIEWICZ, Z
通讯作者：
DARZYNKIEWICZ, Z
影响因子：
5.8
作者：
KAPUSCINSKI, J;DARZYNKIEWICZ, Z
通讯作者：
DARZYNKIEWICZ, Z
DOI：
10.1073/pnas.81.23.7368
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
KAPUSCINSKI, J;DARZYNKIEWICZ, Z
通讯作者：
DARZYNKIEWICZ, Z
影响因子：
12.4
作者：
Reipert, S;Bennion, G;Allen, TD
通讯作者：
Allen, TD