Mouse WRN Helicase Domain Is Not Required for Spontaneous Homologous Recombination-Mediated DNA Deletion

Abstract

Werner syndrome is a rare disorder that manifests as premature aging and age-related diseases.WRNis the gene mutated in WS, and is one of five human RecQ helicase family members. WS cells exhibit genomic instability and altered proliferation, andin vitrostudies suggest that WRN has a role in suppressing homologous recombination. However, more recent studies propose that other RecQ helicases (including WRN) promote early events of homologous recombination. To study the role of WRN helicase on spontaneous homologous recombination, we obtained a mouse with a deleted WRN helicase domain and combined it with thein vivopink-eyed unstable homologous recombination system. In this paper, we demonstrate that WRN helicase is not necessary for suppressing homologous recombinationin vivocontrary to previous reports using a similar mouse model.