نبذة مختصرة : The Structural Maintenance of Chromosomes (SMC) protein family harbors cohesin, condensin and the SMC5/6 complex. SMC5/6 plays critical roles in preserving genome stability by regulating DNA repair, replication, and chromatin organization but its mode of action is not well understood. In this work, we investigated SMC5/6 functions in DNA homeostasis and genome organization by using integrative approaches including RNA-seq, Hi-C, and BLISS analyses. We uncovered functional interplay between SMC5/6 and BRCA1 in genome maintenance and common roles in limiting inflammatory response activation. Our results show that loss of SMC5/6 or BRCA1 induces genomic instability characterized by replication stress, fork degradation and double-strand breaks (DSBs), triggering activation of the cGAS/STING pathway and pro-inflammatory signaling. This is linked to increased micronuclei formation, nuclear envelope fragility, and defects in chromatin architecture. Genome-wide Hi-C analysis revealed that SMC5/6 depletion disrupts ...
Processing Request
No Comments.