Advancing Epigenetics Towards Systems Biology


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Term Definition
Deoxyribonucleic acid, the chemical molecule representing our genes and those of all other organisms. It is made up from a double-helically coiled sugar-phosphate backbone, held together by organic base pairs (adenine with thymine; guanine with cytosine). This generates two complementary strands of base-pairs. The entire sequence of the human genome contains billions of base-pairs.
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DNA damage
The main types of chemical damage arise spontaneously from endogenous processes such as mitochondrial respiration leaking out oxygen radicals (superoxide and peroxides). These can cause oxidation, alcylation or hydrolysis of bases. At sites of base loss the deoxyribose residues exist in equilibrium between the closed furanose form and the open aldehyde form. The 3' phosphodiester bonds are readily hydrolyzed by a β-elimination reaction producing single-strand breaks. Further, double-strand breaks (i.e. two nearby single-strand breaks) can be caused by replication fork collapse, endonuclease activity and radiation. Some DNA repair proteins such as RecA, Rad50, Nbs1, Mre11 or Fen1 are among the most ancient proteins and may date back to the earliest replicators near the origin of life.
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DNA methylation
A reversible biochemical modification of DNA more or less universally present in organisms from bacteria to humans. Methyl groups can be enzymatically added to or removed from cytosine (C). Associated with silencing of DNA sequences.
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DNA repair genes
DNA repair genes encode enzymes which fix DNA damage. Different repair genes function in homologous recombination or double-strand break (DSB) repair (e.g. RecA, Rad50/SMC complex) encompassing non homologous end joining (NHEJ), break-induced replication (BIR), single strand annealing (SSA) and Synthesis-Dependent Strand Annealing (SDSA). Further, in nucleotide excision repair (NER)(e.g. XPD), in base excision repair (BER)(e.g. TDG-glycosylase), mismatch repair (e.g. msh2), damage reversal (e.g. CPD photolyase), damage tolerance (e.g. Rad6), checkpoint-regulatory genes (e.g. RecQ helicases, Rad17, ATM, PARP), DNA polymerases and others like p53.
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DNA replication
The process whereby a cell makes second identical copy of its DNA in preparation for cell division.
DNA sequence
The sequence of bases in 5'->3' direction (printed left to right) along a strand of DNA. There are four organic bases, adenine (A), thymine (T), guanine (G) and cytosine (C) defining the sequence in a single strand DNA. The DNA sequence of a gene will determine the amino-acid composition of a protein.
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A term used to describe the early life stage of a developing organism after fertilization. In humans, the embryo begins after fertilization of an oocyte by a sperm cell and persists up until week 14 of pregnancy.
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Embryonic lethality
Death of an embryo/foetus in the womb. Embryonic lethal genes were first systematically characterized in Drosophila by Eric Wieschaus and Christiane Nüsslein-Volhard. They received a Nobel-Prize in Physiology or Medicine, 1995 for the discovery of the genes involved in the developmental program of the fruit fly.
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Embryonic stem (ES) cells
ES cells are self-renewing cells isolated from the vertebrate inner cell mass of a developing embryo. As ES cells are totipotent they are capable of differentiating into any somatic cell or tissue but they also preserve their capability to remain within the developmental pathway of germ cells. Thus, they are part of the germline.
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Triploid tissue (containing three sets of homologous chromosomes) found in the seeds of flowering plants. It provides nutrition to the developing embryo. It is mostly composed of starch, though it can also contain oils and protein. The cells are formed from a double-fertilization event involving two female nuclei and one male nucleus.
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A protein that facilitates a specific biochemical reaction. Many enzymes work together to build-up and break down biomolecules within the cell. The most central and probably most ancient biochemical pathway driven by enzymes is the citric-acid-cycle. Enzymes also drive transcription, translation, and DNA maintenance.
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The theory that development of an organism, and in particular the development of a plant or animal from an egg or spore through a sequence of gradual steps in which cells differentiate and organs form - a process of increasing complexity. Counter-argument to preformationism, which holds that the whole organism is already present in the sex cells, and merely gets bigger over time.
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Epigenetic code
Both DNA methylation and histone modifications specifically modify the way that genes are expressed. This has led to the theory that there is an epigenetic code which serves to fine-tune the genetic code engraved in the DNA sequence.
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Epigenetic inheritance
The transmission of information from a cell or multicellular organism to its descendants without that information being encoded in the nucleotide sequence of the gene.
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Epigenetic landscape
Conrad Waddington’s visual analogy for the way cells make decisions during development; the cell can take one of several permitted pathways leading to different cell fates (or cell types)