Title: Cardelino: computational integration of somatic clonal substructure and single-cell transcriptomes
Authors: McCarthy, DJ
Rostom, R
Huang, YH
Kunz, DJ
Danecek, P
Bonder, MJ
Hagai, T
Lyu, RQ
Wang, WY
Gaffney, DJ
Simons, BD
Stegle, O
Teichmann, SA
Issue Year: 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 purified monoubiquitinated FANCI: FANCD2 forms filament-like arrays on long dsDNA. Our results reveal how monoubiquitinated FANCI:FANCD2, defective in many cancer types and all cases of FA, is activated upon DNA binding.
URI: https://publications.svi.edu.au/publications/7317
Other Identifiers 10.1038/s41592-020-0766-3
Publication type Article