Advancing Epigenetics Towards Systems Biology

DNA damage

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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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