Abstract

One of the largely unexplored realms in the DNA repair domain pertains to how cells resume their cellular activities following DNA damage repair. Previous research has illuminated the impact of UV damage on nucleolar organization. Specifically, during DNA repair, both nucleolar DNA and RNA polymerase 1 are displaced to the periphery of the nucleolus. However, the restoration of a normal nucleolar structure is not a passive phenomenon and necessitates the involvement of numerous molecular actors that remain unidentified.

We have delved into the role of SMN in nucleolar reorganization during and after the repair of UV-induced damage. Through a blend of live cell imaging and cellular and biochemical approaches, we have demonstrated that in the absence of functional SMN, RNA Polymerase 1 does not return inside the nucleolus post DNA repair, even upon complete restoration of transcription. Moreover, throughout DNA repair, SMN relocates from Cajal Bodies to the nucleolus. Interestingly, this shuttling process is contingent upon physical interactions with Fibrillarin and Coilin and the activity of PRMT1.

Taken together, our study offers a deeper comprehension of the molecular and spatial reorganization of the nucleolus following UV-induced damage. Our findings notably unveil a novel function of SMN in this process and hold the potential to introduce a ribosomal-defect component to SMA disease, a well-known autosomal recessive neuromuscular disorder caused by mutations in the SMN protein.

https://inmg.fr/

Contact GIGA : Denis Mottet