期刊
NUCLEIC ACIDS RESEARCH
卷 41, 期 19, 页码 -出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkt753
关键词
-
资金
- Centre National de la Recherche Scientifique (CNRS) [ATIP]
- Region Midi Pyrenees [Equipe d'Excellence]
- Region Midi Pyrenees [FEDER CNRS/Region Midi Pyrenees]
- CNRS, France
DNA methylation is an important epigenetic mark in eukaryotes, and aberrant pattern of this modification is involved in numerous diseases such as cancers. Interestingly, DNA methylation is reversible and thus is considered a promising therapeutic target. Therefore, there is a need for identifying new small inhibitors of C5 DNA methyltransferases (DNMTs). Despite the development of numerous in vitro DNMT assays, there is a lack of reliable tests suitable for high-throughput screening, which can also give insights into inhibitor mechanisms of action. We developed a new test based on scintillation proximity assay meeting these requirements. After optimizing our assay on human DNMT1 and calibrating it with two known inhibitors, we carried out S-Adenosyl-L-Methionine and DNA competition studies on three inhibitors and were able to determine each mechanism of action. Finally, we showed that our test was applicable to 3 other methyltransferases sources: human DNMT3A, bacterial M. SssI and cellular extracts as well.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据