ATP-dependent helicase activity is dispensable for the physiological functions of Recql4

by Wilson Castillo-Tandazo, Monique F. Smeets, Vincent Murphy, Rui Liu, Charlotte Hodson, J örg Heierhorst, Andrew J. Deans, Carl R. Walkley Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by skin rash (poikiloderma), skeletal dysplasia, small stature, juvenile cataracts, sparse or absent hair, and predisposition to specific malignancies such as osteosarcoma and hematological neoplasms. RTS is cause d by germ-line mutations inRECQL4, a RecQ helicase family member.In vitro studies have identified functions for the ATP-dependent helicase of RECQL4. However, its specific rolein vivo remains unclear. To determine the physiological requirement and the biological functions of Recql4 helicase activity, we generated mice with an ATP-binding-deficient knock-in mutation (Recql4K525A).Recql4K525A/K525A mice were strikingly normal in terms of embryonic development, body weight, hematopoiesis, B and T cell development, and physiological DNA damage repair. However, mice bearing two distinct truncating mutationsRecql4G522Efs andRecql4R347*, that abolished not only the helicase but also the C-terminal domain, developed a profound bone marrow failure and decrease in survival similar to aRecql4 null allele. These results demonstrate that the ATP-dependent helicase activity of Recql4 is not essential for its physiological functions and that other domains might contribute to this phenotype. Future studies need to be performed to elucidate the complex intera...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research