Journal article
Mechanism of Ubiquitination and Deubiquitination in the Fanconi Anemia Pathway
S van Twest, VJ Murphy, C Hodson, W Tan, P Swuec, JJ O'Rourke, J Heierhorst, W Crismani, AJ Deans
Molecular Cell | CELL PRESS | Published : 2017
Abstract
Monoubiquitination and deubiquitination of FANCD2:FANCI heterodimer is central to DNA repair in a pathway that is defective in the cancer predisposition syndrome Fanconi anemia (FA). The “FA core complex” contains the RING-E3 ligase FANCL and seven other essential proteins that are mutated in various FA subtypes. Here, we purified recombinant FA core complex to reveal the function of these other proteins. The complex contains two spatially separate FANCL molecules that are dimerized by FANCB and FAAP100. FANCC and FANCE act as substrate receptors and restrict monoubiquitination to the FANCD2:FANCI heterodimer in only a DNA-bound form. FANCA and FANCG are dispensable for maximal in vitro ubiq..
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Awarded by Fanconi Anemia Research Fund
Funding Acknowledgements
We thank Alexandra Sobeck, Puck Knipscheer, Steve West, Johan de Winter, K.J. Patel, Paul Hasty, Dario Alessi, Kum Kum Khanna, Timothy Richmond, and Simon Boulton for reagents. A.J.D. received fellowships from the National Breast Cancer Foundation (Australia) and the Victorian Cancer Agency. W.C. is a Maddie Riewoldt's Vision fellow. J.J.O. and P.S. respectively received scholarships from the Leukaemia Foundation (Australia) and Cancer Research UK. J.H. was a National Health and Medical Research Council (NHMRC) Senior Research Fellow (1022469). This work was funded by the Fanconi Anemia Research Fund, as well as Perpetual Trustees, Cancer Council of Victoria, SVI Breakthrough, and the Victorian Government's OIS Program.