Enigmatic role of WRN-RECQL helicase in DNA repair and its implications in cancer

Werner (WRN) helicase belongs to the RECQL class of DNA helicases. Mutation in Werner (WRN) RECQL helicase leads to premature aging syndrome, Werner syndrome (WS), and predisposition to multiple cancers. WS patients exhibit heightened incidence of neoplasia, e.g., soft tissue sarcoma, osteosarcoma, malignant melanoma, meningioma, thyroid cancer, breast cancer, and leukemias. Extensive research on WRN helicase has revealed its important and diverse roles in DNA repair pathways, especially in double-strand break repair. Consequently, WRN deficiency is causally associated with genomic instability and cancer predispositions. In this review, we summarize recent studies unraveling the fundamental roles WRN helicase plays in DNA repair and genome stability and its implications in cancer therapy and resistance.