SUMO-Based Regulation of Nuclear Positioning to Spatially Regulate Homologous Recombination Activities at Replication Stress Sites

DNA lesions have properties that allow them to escape their nuclear compartment to achieve DNA repair in another one. Recent studies uncovered that the replication fork, when its progression is impaired, exhibits increased mobility when changing nuclear positioning and anchors to nuclear pore complexes, where specific types of homologous recombination pathways take place. In yeast models, increasing evidence points out that nuclear positioning is regulated by small ubiquitin-like modifier (SUMO) metabolism, which is pivotal to maintaining genome integrity at sites of replication stress. Here, we review how SUMO-based pathways are instrumental to spatially segregate the subsequent steps of homologous recombination during replication fork restart. In particular, we discussed how routing towards nuclear pore complex anchorage allows distinct homologous recombination pathways to take place at halted replication forks.

Automated summary

DNA lesions can escape their nuclear compartment for repair, while impaired replication forks demonstrate increased mobility and anchor to nuclear pore complexes for specific forms of homologous recombination pathways. Research suggests that SUMO metabolism regulates nuclear positioning, crucial for maintaining genome integrity during replication stress, and is integral to segregating homologous recombination steps during replication fork restart. Routing towards nuclear pore complex anchorage facilitates distinct homologous recombination pathways at stalled replication forks.