Journal article

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

Wilson Castillo-Tandazo, Monique F Smeets, Vincent Murphy, Rui Liu, Charlotte Hodson, Joerg Heierhorst, Andrew J Deans, Carl R Walkley

PLOS Genetics | PUBLIC LIBRARY SCIENCE | Published : 2019

Abstract

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 caused by germ-line mutations in RECQL4, a RecQ helicase family member. In vitro studies have identified functions for the ATP-dependent helicase of RECQL4. However, its specific role in 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/K525..

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Grants

Awarded by Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Cancer Research


Awarded by National Health and Medical Research Council Australia project grant (NHMRC)


Awarded by Victorian Cancer Agency Research Fellowship


Funding Acknowledgements

This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Cancer Research under Award No. W81XWH-15-1-0315 (to CRW). Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense (USA); National Health and Medical Research Council Australia project grant (NHMRC; CRW and AJD, APP1102004); a Melbourne Research Scholarship (WCT, University of Melbourne); Victorian Cancer Agency Research Fellowship (CRW, MCRF15015; AJD, MCRF15024); This work was enabled by the Australian Phenomics Network and partly supported by funding from the Australian Government's National Collaborative Research Infrastructure Strategy and the Super Science Initiative through the Education Investment Fund (to Australian Phenomics Network); and in part by the Victorian State Government Operational Infrastructure Support (to St Vincent's Institute). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.