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

从细菌到人类的所有生物体的一个基本特性是通过修复DNA来纠正遗传错误的能力。 在多细胞生物体中，发现DNA与组蛋白一起包装在细胞核中以形成染色质。当DNA被包装到染色质中时，DNA的损伤更难被发现和修复。然而，染色质中的一种组蛋白被磷酸化（称为γ-H2 A.X），标记染色质进行DNA修复，并产生光镜下可见的点状斑点或病灶。这些“修复灶”被认为是招募修复DNA的酶的召唤物。修复灶有时与细胞核的特定亚区或结构域相关，例如早幼粒细胞白血病核体（PML NB）和核纤层。尽管修复灶由于与γ-H2 A.X共定位而在鉴定新的DNA修复因子方面非常有用，但我们对它们的超微结构或它们在核中的结构或位置的变化如何与DNA修复过程相关几乎一无所知。

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.