Medical Toxicology Commons^™

Replication Fork Regression In Vitro By The Werner Syndrome Protein (Wrn): Holliday Junction Formation, The Effect Of Leading Arm Structure And A Potential Role For Wrn Exonuclease Activity, Amrita Machwe, Liren Xiao, Robert G Lloyd, Edward Bolt, David K. Orren

Toxicology and Cancer Biology Faculty Publications

The premature aging and cancer-prone disease Werner syndrome stems from loss of WRN protein function. WRN deficiency causes replication abnormalities, sensitivity to certain genotoxic agents, genomic instability and early replicative senescence in primary fibroblasts. As a RecQ helicase family member, WRN is a DNA-dependent ATPase and unwinding enzyme, but also possesses strand annealing and exonuclease activities. RecQ helicases are postulated to participate in pathways responding to replication blockage, pathways possibly initiated by fork regression. In this study, a series of model replication fork substrates were used to examine the fork regression capability of WRN. Our results demonstrate that WRN catalyzes …