| 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 |
| Publisher | NATURE RESEARCH |
| Series | NATURE METHODS: |
| 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 |