Nuclear domains and DNA Repair

The eukaryotic genome is being constantly subjected to DNA damage arising from environmental and endogenous mutagens. Rapid and faithful repair of damaged DNA is an essential process to life, and in multicellular organisms the presence of irreparable DNA damage induces cell cycle arrest to prevent propagation of a damaged genome, which can lead to cancer. DNA repair is mediated by the DNA damage response, a network of proteins that sense, signal, and repair through the ordered recruitment of DNA repair factors to sites of damage. Repair of DNA occurs in discrete regions of the nucleus called DNA repair foci, whose composition and localization to various nuclear subdomains depends on the stage of DNA repair and the severity of damage. In this chapter we will discuss two nuclear subdomains, the nuclear lamina, and promyelocytic leukemia nuclear bodies (PML-NBs), and how the DNA damage response is regulated at these domains.