SUMOylation of CLIP (chromatin linkage of INM protein) controls rDNA stability

CAPELLA, MATIAS; BRAUN, SIGURD; JENTSCH, STEFAN

Illkirch

Workshop; Chromatin dynamics and nuclear organization in genome maintenance; 2018

European Molecular Biology Organization

Maintaining genome integrity is essential for cellular viability. Due to its repetitive nature, the rDNA locus often undergoes homologous recombination (HR), resulting in gain or loss of individual repeats. Uncontrolled recombination is suppressed by restricting the rDNA repeats to the nuclear periphery within the nucleolus, preventing access to the HR machinery. Following double-strand breaks, the damaged rDNA repeat thus needs to be relocalized out of the nucleolus, a process that is conserved from yeast to humans. However, the molecular mechanism controlling rDNA relocalization and repair remains unknown. We found that, in S. cerevisiae, the inner nuclear membrane protein Nur1, a member of the CLIP-cohibin complex involved in rDNA tethering, is SUMOylated. SUMOylation of Nur1 depends on the conserved SUMO E3 ligase Siz2 and is induced upon cohesin depletion. We observed that the absence of Nur1 SUMOylation increases the association between CLIP and cohibin. Moreover, replacing Nur1 with the SUMO-deficient mutant resulted in a decrease of rDNA copy number while increasing repeats stability. In conclusion, our findings reveal SUMOylation of CLIP as a molecular switch that regulates tethering of the rDNA repeats at the nuclear periphery to maintain genome stability.