WRN (81)

WRN (Werner syndrome helicase), a member of the RecQ DNA helicase subfamily, plays a crucial role in various DNA processing activities such as DNA replication, double-strand break repair, transcription, and telomere maintenance, earning its reputation as a "genome caretaker." Research has identified WRN helicase as a synthetic lethal target in cancer cells exhibiting microsatellite instability (MSI), a condition of genetic hypermutability caused by defective mismatch repair. MSI, characterized by a high mutational burden, is found in over 20 types of tumors and is particularly common in colon, ovarian, endometrial, and gastric cancers. WRN depletion in MSI cells triggers extensive DNA double-strand breaks, resulting in cell cycle arrest and/or apoptosis. Therefore, targeting WRN helicase presents a promising therapeutic approach for treating cancers with mismatch repair deficiencies.