Rennie, M. L. , Lemonidis, K. , Arkinson, C., Chaugule, V. K. , Clarke, M. , Streetley, J. , Spagnolo, L. and Walden, H. (2020) Differential functions of FANCI and FANCD2 ubiquitination stabilize ID2 complex on DNA. EMBO Reports, 21(7), e50133. (doi: 10.15252/embr.202050133) (PMID:32510829) (PMCID:PMC7332966)
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Abstract
The Fanconi anaemia (FA) pathway is a dedicated pathway for the repair of DNA interstrand crosslinks and is additionally activated in response to other forms of replication stress. A key step in the FA pathway is the monoubiquitination of each of the two subunits (FANCI and FANCD2) of the ID2 complex on specific lysine residues. However, the molecular function of these modifications has been unknown for nearly two decades. Here, we find that ubiquitination of FANCD2 acts to increase ID2's affinity for double‐stranded DNA via promoting a large‐scale conformational change in the complex. The resulting complex encircles DNA, by forming a secondary “Arm” ID2 interface. Ubiquitination of FANCI, on the other hand, largely protects the ubiquitin on FANCD2 from USP1‐UAF1 deubiquitination, with key hydrophobic residues of FANCI's ubiquitin being important for this protection. In effect, both of these post‐translational modifications function to stabilize a conformation in which the ID2 complex encircles DNA.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Spagnolo, Dr Laura and Clarke, Dr Mairi and Chaugule, Dr Viduth and Streetley, Dr James and Lemonidis, Dr Kimon and Arkinson, Connor and Rennie, Dr Martin and Walden, Professor Helen |
| Authors: | Rennie, M. L., Lemonidis, K., Arkinson, C., Chaugule, V. K., Clarke, M., Streetley, J., Spagnolo, L., and Walden, H. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Molecular Biosciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | EMBO Reports |
| Publisher: | Wiley |
| ISSN: | 1469-221X |
| ISSN (Online): | 1469-3178 |
| Published Online: | 08 June 2020 |
| Copyright Holders: | Copyright © 2020 The Authors |
| First Published: | First published in EMBO Reports 21(7): e50133 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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