Nucleolar Dynamic during DNA Repair in action (Nu-DyRection)

The nucleolus is a membrane-less nuclear compartment with a highly ordered internal organization, tightly linked to its main role in ribosome biogenesis. This includes the transcription of ribosomal DNA (rDNA) by RNA polymerase I (RNAP1) and the early maturation of ribosomal RNA.
This sophisticated organization can be severely disrupted by genotoxic agents or by general cellular stress. In recent years, our work has shown that following genotoxic stress such as ultraviolet (UV) irradiation, RNA polymerase I and ribosomal DNA are relocated to the nucleolar periphery. Remarkably, nucleolar architecture is only restored once all rDNA lesions – in both active and inactive regions – have been repaired.
Complete restoration of the nucleolus therefore depends not only on efficient DNA repair systems, but also on the action of key proteins. Among these, the SMN protein (Survival of Motor Neuron), which is defective in patients with spinal muscular atrophy (SMA), plays a central role. We have demonstrated that in the absence of SMN, RNA polymerase I remains trapped at the nucleolar periphery even after DNA damage repair is completed. Strikingly, SMN translocates from Cajal bodies (CBs) to the nucleolus immediately after repair, but before nucleolar structure is fully re-established.