Werner Syndrome (WS) is an autosomal-recessive genetic disorder characterized by premature ageing and DNA repair defects because of mutations in the WRN gene. WRN is a RecQ family protein with helicase, strand annealing and exonuclease activities. WRN localizes to the sites of damaged DNA, interacts with several DNA repair pathways including base excision DNA repair, non-homologous end-joining (NHEJ), homologous recombination (HR) and replication re-start after DNA damage.
Here, we constructed an experimental cascade from in vitro to in vivo, which is composed of protein production, biochemical assays, cell line construction, cellular assays, and animal modeling. This WRN screening cascade can satisfy the mechanism study of WRN as well as efficient and comprehensive screen of WRN inhibitor, thus accelerate the novel drug discovery.
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