HRO761

The WRN gene was first discovered as the gene mutated in Werner syndrome, a recessive genetic disorder characterized by segmental progeria and elevated cancer predisposition. WRN is a multifunctional enzyme with helicase and exonuclease activities and plays roles in various cellular processes crucial for the maintenance of genome stability, including DNA replication, transcription, DNA repair, and telomere maintenance. WRN depletion causes cell cycle arrest, DNA damage, mitotic defects, chromosome shattering, and apoptosis. Loss of heterozygosity involving theWRNloci at chromosome 8p11.2-p12 occurs frequently in many different cancers, pointing to its role as a tumor suppressor gene. Small molecule inhibitors of WRN can be used to induce synthetic lethality and offer a new therapeutical approach for cancer treatment.