Abstract
Early screens in yeast for mutations exhibiting sensitivity to DNA damage identified nuclear pore components, but their role in DNA repair was not well understood. Over the last decade, studies have revealed that several types of persistent DNA lesions relocate to either the nuclear pore complex (NPC) or nuclear envelope (NE). Of these two sites, the nuclear pore appears to be crucial for DNA repair of persistent double-strand breaks, eroded telomeres and sites of fork collapse at expanded CAG repeats. Using a combination of cell biological imaging techniques and yeast genetic assays for DNA repair, researchers have begun to understand both the how and why of lesion relocation to the NPC. Here we review the types of lesions that relocate to the NPC, mediators of relocation and the functional consequences of relocation understood to date. The emerging theme is that relocation to the NPC regulates recombination to influence repair pathway choice and provide a rescue mechanism for lesions or DNA structures that are resistant to repair.
Highlights
DNA repair must occur in the context of a crowded nucleus
The Slx5/8 complex provides an intriguing link between on-site sumoylation at DNA lesions and relocation to the nuclear pore complex (NPC), as it interacts with Nup84, and mediates relocation of each of the lesions shown to interact with the nuclear pore tested to date, including an expanded CAG tract, eroded telomere and persistent double-strand break (DSB) (Table 1) (Nagai et al 2008; Su et al 2015; Churikov et al 2016; Horigome et al 2016)
These studies in yeast have elucidated an important role for movement of chromosomes between different nuclear compartments to facilitate DNA repair and regulate pathway choice
Summary
For homologous recombination (HR), the additional challenge exists of finding the right homologous template for repair This is facilitated by robust search mechanisms, including proteins such as Rad that mediate synapsis (Symington, Rothstein and Lisby 2014) and a regulated increase in mobility of the broken chromosome (Dion et al 2012; Mine-Hattab and Rothstein 2012; Dion and Gasser 2013). Some types of damage appear to be more difficult to repair, and can persist, Received: 21 July 2016; Accepted: 27 October 2016 C FEMS 2016.
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