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Bernstein, B. E., Meissner, A., & Lander, E. S. (2007). The mammalian epigenome. Cell, 128(4), 669–681.
Abstract: Chemical modifications to DNA and histone proteins form a complex regulatory network that modulates chromatin structure and genome function. The epigenome refers to the complete description of these potentially heritable changes across the genome. The composition of the epigenome within a given cell is a function of genetic determinants, lineage, and environment. With the sequencing of the human genome completed, investigators now seek a comprehensive view of the epigenetic changes that determine how genetic information is made manifest across an incredibly varied background of developmental stages, tissue types, and disease states. Here we review current research efforts, with an emphasis on large-scale studies, emerging technologies, and challenges ahead.
Keywords: Animals; Chromatin Assembly and Disassembly/*genetics; CpG Islands/genetics; DNA Methylation; Epigenesis, Genetic/*genetics; Gene Expression Regulation, Developmental/genetics; Genomic Instability/*genetics; Histones/genetics/metabolism; Humans; Mammals/*genetics
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Binhi, V. (2008). Do naturally occurring magnetic nanoparticles in the human body mediate increased risk of childhood leukaemia with EMF exposure? Int J Radiat Biol, 84(7), 569–579.
Abstract: PURPOSE: To develop the hypothesis that magnetic nanoparticles, found in many organisms and often involved in biological reactions to weak electromagnetic fields (EMF), mediate EMF-induced DNA damage which could result in increased risk of childhood leukaemia and other cancers. MATERIALS AND METHODS: An analysis of current research into magnetic nanoparticles. Physics estimates and the development of the hypothesis that intracellular magnetic nanoparticles chronically change the free radical concentration and can mediate the enhanced rate of DNA damage in hematopoietic stem cells. RESULTS: The properties of magnetic nanoparticles are considered and the naturally occurring magnetic field generated by a magnetic nanoparticle within a cell is calculated to be in the range of about 1-200 millitesla, which exceeds the level of the natural geomagnetic field by orders of magnitude. Experiments are summarized on the biological effects of static magnetic field in this range. It is shown that magnetic nanoparticles can increase the rate of free radical formation by a few percent, in the course of an idealized radical-pair reaction in a cell. A mechanism is discussed that explains how weak alternating magnetic fields, of the order of 0.4 muT, could cause an increase in the rate of leukaemia via millitesla fields produced around superparamagnetic nanoparticles in hematopoietic stem cells. CONCLUSIONS: The postulated presence of magnetic nanoparticles located in hematopoietic stem cells could constitute a cancer risk factor. Superparamagnetic nanoparticles can possibly mediate increased level of leukaemia caused by background exposure to low-frequency weak EMF.
Keywords: Child; DNA Damage/physiology/*radiation effects; Electromagnetic Fields/*adverse effects; Free Radicals/metabolism/radiation effects; Hematopoietic Stem Cells/cytology/physiology/*radiation effects; Humans; *Leukemia, Radiation-Induced; Magnetics/*adverse effects; Nanoparticles/*adverse effects; Risk Factors; Time Factors; *Whole-Body Irradiation
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Biskup, T., Hitomi, K., Getzoff, E. D., Krapf, S., Koslowski, T., Schleicher, E., et al. (2011). Unexpected Electron Transfer in Cryptochrome Identified by Time-Resolved EPR Spectroscopy. Angew. Chem. Int. Ed., 50(52), 12647–12651.
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Biskup, T., Paulus, B., Okafuji, A., Hitomi, K., Getzoff, E. D., Weber, S., et al. (2013). Variable Electron Transfer Pathways in an Amphibian Cryptochrome: TRYPTOPHAN VERSUS TYROSINE-BASED RADICAL PAIRS. J Biol Chem, 288(13), 9249–9260.
Abstract: Electron transfer reactions play vital roles in many biological processes. Very often the transfer of charge(s) proceeds stepwise over large distances involving several amino acid residues. By using time-resolved electron paramagnetic resonance and optical spectroscopy, we have studied the mechanism of light-induced reduction of the FAD cofactor of cryptochrome/photolyase family proteins. In this study, we demonstrate that electron abstraction from a nearby amino acid by the excited FAD triggers further electron transfer steps even if the conserved chain of three tryptophans, known to be an effective electron transfer pathway in these proteins, is blocked. Furthermore, we were able to characterize this secondary electron transfer pathway and identify the amino acid partner of the resulting flavin-amino acid radical pair as a tyrosine located at the protein surface. This alternative electron transfer pathway could explain why interrupting the conserved tryptophan triad does not necessarily alter photoreactions of cryptochromes in vivo. Taken together, our results demonstrate that light-induced electron transfer is a robust property of cryptochromes and more intricate than commonly anticipated.
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Bock, J., Fukuyo, Y., Kang, S., Phipps, M. L., Alexandrov, L. B., Rasmussen, K. Ã. ˜., et al. (2010). Mammalian Stem Cells Reprogramming in Response to Terahertz Radiation. PLoS ONE, 5(12), e15806.
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