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
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..View full abstract
Awarded by Maddie Riewoldt's Vision
Awarded by National Health and Medical Research Council
Awarded by National Breast Cancer Foundation
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.