Journal article

Monoubiquitination by the human Fanconi anemia core complex clamps FANCI: FANCD2 on DNA in filamentous arrays

Winnie Tan, Sylvie van Twest, Andrew Leis, Rohan Bythell-Douglas, Vincent J Murphy, Michael Sharp, Michael W Parker, Wayne Crismani, Andrew J Deans

eLife | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2020

Abstract

FANCI:FANCD2 monoubiquitination is a critical event for replication fork stabilization by the Fanconi anemia (FA) DNA repair pathway. It has been proposed that at stalled replication forks, monoubiquitinated-FANCD2 serves to recruit DNA repair proteins that contain ubiquitin-binding motifs. Here, we have reconstituted the FA pathway in vitro to study functional consequences of FANCI:FANCD2 monoubiquitination. We report that monoubiquitination does not promote any specific exogenous protein:protein interactions, but instead stabilizes FANCI:FANCD2 heterodimers on dsDNA. This clamping requires monoubiquitination of only the FANCD2 subunit. We further show using electron microscopy that purifie..

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Awarded by Maddie Riewoldt's Vision


Awarded by National Health and Medical Research Council


Awarded by National Breast Cancer Foundation


Funding Acknowledgements

Fanconi Anemia Research Fund Wayne Crismani Andrew J DeansMaddie Riewoldt's Vision SVI-MRV2017G Wayne CrismaniVictorian Government OIS Program Winnie Tan Sylvie van Twest Rohan Bythell-Douglas Vincent J Murphy Michael Sharp Michael W Parker Wayne Crismani Andrew J DeansVictorian Cancer Agency Andrew J DeansNational Health and Medical Research Council GNT1123100 Andrew J DeansNational Health and Medical Research Council GNT1156343 Wayne CrismaniNational Health and Medical Research Council GNT1117183 Michael W ParkerNational Breast Cancer Foundation IIRS-19-017 Rohan Bythell-Douglas Andrew J DeansAustralian Government Research Training Program Winnie TanNational Health and Medical Research Council GNT1129757 Wayne CrismaniNational Health and Medical Research Council GNT1181110 Andrew J DeansMaddie Riewoldt's Vision MRV2016 Wayne CrismaniThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.