Insights into Fanconi Anaemia from the structure of human FANCE
Nucleic Acids Research
Oxford University Press
MetadataShow full item record
Nookala, R., Hussain, S., & Pellegrini, L. (2007). Insights into Fanconi Anaemia from the structure of human FANCE. Nucleic Acids Research, 35 (5), 1638-1648. https://doi.org/10.1093/nar/gkm033
Fanconi Anaemia (FA) is a cancer predisposition disorder characterized by spontaneous chromosome breakage and high cellular sensitivity to genotoxic agents. In response to DNA damage, a multi-subunit assembly of FA proteins, the FA core complex, monoubiquitinates the downstream FANCD2 protein. The FANCE protein plays an essential role in the FA process of DNA repair as the FANCD2-binding component of the FA core complex. Here we report a crystallographic and biological study of human FANCE. The first structure of a FA protein reveals the presence of a repeated helical motif that provides a template for the structural rationalization of other proteins defective in Fanconi Anaemia. The portion of FANCE defined by our crystallographic analysis is sufficient for interaction with FANCD2, yielding structural information into the mode of FANCD2 recruitment to the FA core complex. Disease-associated mutations disrupt the FANCE-FANCD2 interaction, providing structural insight into the molecular mechanisms of FA pathogenesis.
complex, protein, DNA-repair, network, PATHWAY, brca1, BRCA2/FANCD1, ORTHOLOG, REVEALS, UBIQUITIN LIGASE
This work was supported by a Wellcome Trust senior research fellowship award to L.P. Atomic coordinates and structure factors have been deposited in the RCS PDB with accession code: 2ILR. Funding to pay the Open Access Publication change was provided by The Wellcome Trust.
Wellcome Trust (071102/Z/03/Z)
External DOI: https://doi.org/10.1093/nar/gkm033
This record's URL: https://www.repository.cam.ac.uk/handle/1810/263596
Attribution-NonCommercial 4.0 International, Attribution-NonCommercial 4.0 International, Attribution-NonCommercial 4.0 International, Attribution-NonCommercial 4.0 International