Structure and function of the nucleus in DNA damage signaling and repair

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A fundamental property of all living organisms from bacteria to humans, is the ability to correct genetic errors by repairing DNA. In multicellular organisms, DNA is found in the nucleus packaged with histone proteins to form chromatin. Damage to DNA is more difficult to find and repair when it is packaged into chromatin. However, one of the histone proteins in chromatin becomes phosphorylated (termed gamma-H2A.X), marking that chromatin for DNA repair and producing punctate spots or foci that can be seen with a light microscope. These "repair foci" are believed to act as beckons for the recruitment of enzymes that repair DNA. Repair foci are sometimes associated with particular sub-regions or domains of the nucleus such as the promyelocytic leukemia nuclear body (PML NB) and the nuclear lamina. Although repair foci have been immensely useful in the identification of novel DNA repair factors by virtue of their co-localisation with gamma-H2A.X, we know virtually nothing about their ultrastructure or how changes in their structure or location in the nucleus relate to the process of DNA repair.