Lack of WRN Results in Extensive Deletion at Nonhomologous Joining Ends

Loss of WRN causes the genomic instability progeroid syndrome, Werner syndrome. WRN encodes a multifunctional nuclear protein with 3′→5′ exonuclease and 3′→5′helicase activities. Linear plasmids with noncompatible ends introduced to Werner syndrome cells underwent extensive deletions at nonhomologous joining ends, particularly at the 3′ protruding single-stranded end. This extensive deletion phenotype was complemented by wild-type WRN . These results suggest that WRN can out-compete other exonucleases that participate in double-strand break repair or stabilize the broken DNA end.