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Newly found enzymes may play early role in cancer
December 29, 2008Zebrafish study suggests new targeted treatment
SALT LAKE CITY-Researchers have discovered two enzymes that, when combined, could be involved in the earliest stages of cancer. Manipulating these enzymes genetically might lead to targeted therapies aimed at slowing or preventing the onset of tumors.
"We could conceivably reactivate a completely normal gene in a tumor cell - a gene that could prevent the growth of a tumor if reactivated," says David Jones, Ph.D., professor of oncological sciences at the University of Utah and senior director of early translational research at the university's Huntsman Cancer Institute (HCI).
"We believe this could be one of the earliest processes to go wrong in cancer," he adds. "By manipulating these enzymes, we could possibly prevent or slow the onset of tumors."
The enzymes appear to control an "on-and-off switch" for critical genes that could trigger cancer or numerous other diseases and birth defects. The research is published in the December 26 issue of Cell.
Using zebrafish that share similar genetics to humans, the HCI scientists identified a previously unknown enzyme process that controls the levels of DNA methylation on genes.
"Methylation is a cellular process that is required for healthy cell growth and development, but it can go awry in cancer and diseased cells," says Brad Cairns, Ph.D., HCI investigator and professor of oncological sciences at the University of Utah. "You can think of DNA methylation as an on-and-off switch. Methylation silences or 'shuts off' genes that need to be turned off or are not functioning as they should, whereas the reverse process called demethylation 'turns on' healthy genes and genes needed at critical times in development," he says.
In cancer, this methylation process goes haywire, leading to tumor growth. Genes that should be "turned on" are not and vice versa.
The significance of this research is the discovery of two enzymes involved in DNA demethylation. Defects in DNA methylation balance are strongly associated with the early development of cancer, other diseases and birth defects, and the scientists say their study is the first clear evidence that this enzyme system plays a critical role in maintaining this balance. They also believe it's a process that can be reversed.
Further research will reveal if DNA methylation levels can be manipulated genetically. If so, it could lead to drugs to reactivate particular genes and suppress tumor growth. Remarkably, this system also helps protect the genome from mutations.
"We discovered a pair of enzymes that can remove methylated DNA, but if these enzymes work improperly, they will instead enhance the rate of mutations in methylated DNA and cause cancer progression," says Jones. "The question now is, when they work improperly, can we find ways to shut them off and prevent these mutations?"
The enzymes leading to DNA demethylation involve the coupling of a 5-meC deaminase enzyme, a G:T glycosylase enzyme and Gadd45, which is not an enzyme.
University of Utah
"We believe this could be one of the earliest processes to go wrong in cancer," he adds. "By manipulating these enzymes, we could possibly prevent or slow the onset of tumors."
The enzymes appear to control an "on-and-off switch" for critical genes that could trigger cancer or numerous other diseases and birth defects. The research is published in the December 26 issue of Cell.
Using zebrafish that share similar genetics to humans, the HCI scientists identified a previously unknown enzyme process that controls the levels of DNA methylation on genes.
"Methylation is a cellular process that is required for healthy cell growth and development, but it can go awry in cancer and diseased cells," says Brad Cairns, Ph.D., HCI investigator and professor of oncological sciences at the University of Utah. "You can think of DNA methylation as an on-and-off switch. Methylation silences or 'shuts off' genes that need to be turned off or are not functioning as they should, whereas the reverse process called demethylation 'turns on' healthy genes and genes needed at critical times in development," he says.
In cancer, this methylation process goes haywire, leading to tumor growth. Genes that should be "turned on" are not and vice versa.
The significance of this research is the discovery of two enzymes involved in DNA demethylation. Defects in DNA methylation balance are strongly associated with the early development of cancer, other diseases and birth defects, and the scientists say their study is the first clear evidence that this enzyme system plays a critical role in maintaining this balance. They also believe it's a process that can be reversed.
Further research will reveal if DNA methylation levels can be manipulated genetically. If so, it could lead to drugs to reactivate particular genes and suppress tumor growth. Remarkably, this system also helps protect the genome from mutations.
"We discovered a pair of enzymes that can remove methylated DNA, but if these enzymes work improperly, they will instead enhance the rate of mutations in methylated DNA and cause cancer progression," says Jones. "The question now is, when they work improperly, can we find ways to shut them off and prevent these mutations?"
The enzymes leading to DNA demethylation involve the coupling of a 5-meC deaminase enzyme, a G:T glycosylase enzyme and Gadd45, which is not an enzyme.
University of Utah
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DNA Methylation: Methods and Protocols (Methods in Molecular Biology) by Jörg Tost (Editor) Over the past few years, DNA methylation technologies and our knowledge of DNA methylation patterns have been advancing at a breathtaking pace. Due to this fact, DNA Methylation: Methods and Protocols, Second Edition completely revises, updates, and expands upon the popular first edition with the most current novel techniques, easier to use and more refined by the tested experience of leading experts. This revision reflects contemporary study of the subject: the analysis of gene-specific DNA methylation patterns has been complemented by genome-wide approaches, and epigenomics takes a central place. Written in the highly successful Methods in Molecular Biology™ series format, the chapters in this volume present brief introductions to the topics, lists of the necessary materials and... |
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DNA Methylation Microarrays: Experimental Design and Statistical Analysis (Chapman & Hall/Crc Biostatistics Series) by Sun-Chong Wang (Author), Art Petronis (Author) Providing an interface between dry-bench bioinformaticians and wet-lab biologists, DNA Methylation Microarrays: Experimental Design and Statistical Analysis presents the statistical methods and tools to analyze high-throughput epigenomic data, in particular, DNA methylation microarray data. Since these microarrays share the same underlying principles as gene expression microarrays, many of the analyses in the text also apply to microarray-based gene expression and histone modification (ChIP-on-chip) studies. After introducing basic statistics, the book describes wet-bench technologies that produce the data for analysis and explains how to preprocess the data to remove systematic artifacts resulting from measurement imperfections. It then explores differential methylation and... |
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DNA Methylation: Development, Genetic Disease and Cancer (Current Topics in Microbiology and Immunology) by Walter Doerfler (Editor), P. Böhm (Editor) It has become apparent that the genomes of many organisms are characterized by unique patterns of DNA methylation, which can differ from genome segment to genome segment and cell type to cell type. These patterns can be instrumental in determining cell type and function. Thus, it is not surprising that studies on the role of DNA methylation now occupy center stage in many fields of biology and medicine such as developmental biology, genetic imprinting, genetic disease, tumor biology, gene therapy, cloning of organisms and others. Once again, basic research in molecular biology has provided the essential foundation for investigations of biomedical problems. |
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DNA Methylation Protocols (Methods in Molecular Biology) by Ken I. Mills (Editor), Bernie H. Ramsahoye (Editor) Univ. of Wales, Cardiff, UK. Covers new techniques currently available in the analysis of DNA methylation and methylases. For researchers. |
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DNA Methylation: Approaches and Applications by Manel Esteller (Editor) Understanding the complex roles of DNA methylation is currently an active field of research. DNA Methylation: Approaches and Applications presents the most current research on the impact of DNA methylation in human disease, particularly cancer. Written by leaders in the field, this state-of-art reference delineates the best techniques to use when addressing questions concerning the cytocine methylation status of genomic DNA. It includes concepts, experimental models, and clinical uses of demethylating agents. The book provides a balance between articles clarifying methodological details and more general review chapters that offer broad biological perspectives on DNA methylation. |
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Progress in DNA Methylation Research by Hans P. Neumann (Other Contributor) DNA methylation is a type of chemical modification of DNA that can be inherited without changing the DNA sequence. As such, it is part of the epigenetic code and is the most characterised epigenetic mechanism. DNA methylation involves the addition of a methyl group to DNA - for example, to the number 5 carbon of the cytosine pyrimidine ring. DNA methylation is probably universal in eukaryotes. In humans, approximately 1% of DNA bases undergo DNA methylation. In adult somatic tissues, DNA methylation typically occurs in a CpG dinucleotide context; non-CpG methylation is prevalent in embryonic stem cells. In plants, cytosines are methylated both symmetrically (CpG or CpNpG) and asymmetrically (CpNpNp), where N can be any nucleotide. The methylation status of specific cytosines can be... |
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Molecular Biology of DNA Methylation (Springer Series in Molecular Biology) by Roger L. P. Adams (Author), Roy H. Burdon (Author) | |
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Biochemistry and biology of DNA methylation: Proceedings of a Fogarty International Center conference held in Bethesda, Maryland, April 17-19, 1985 (Progress in clinical and biological research) by Liss (Publisher) |
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