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

从细菌到人类，所有活着的有机体的一个基本属性是通过修复DNA来纠正遗传错误的能力。在多细胞生物中，DNA存在于包有组蛋白的细胞核中，形成染色质。当DNA被包装到染色质中时，对DNA的损伤更难发现和修复。然而，染色质中的一种组蛋白蛋白被磷酸化(称为伽马-H_2A.X)，标记该染色质用于DNA修复，并产生光学显微镜可以看到的点状斑点或焦点。这些“修复焦点”被认为是对修复DNA的酶的招募的召唤。修复灶有时与核的特定亚区或区域有关，如早幼粒细胞白血病核体(PML-NB)和核层。虽然修复灶由于与γ-H_2A.X共定位而在识别新的DNA修复因子方面非常有用，但我们几乎不知道它们的超微结构，也不知道它们在细胞核中的结构或位置的变化如何与DNA修复过程有关。

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.