AI Article Synopsis
- - The monoubiquitination of FANCI:FANCD2 is essential for stabilizing replication forks through the Fanconi anemia DNA repair pathway, particularly at stalled forks.
- - Research indicates that instead of facilitating specific protein interactions, monoubiquitination stabilizes FANCI:FANCD2 heterodimers on double-stranded DNA (dsDNA).
- - Electron microscopy studies reveal that monoubiquitinated FANCI:FANCD2 forms filament-like structures on long dsDNA, providing insight into its activation and role in cancer and Fanconi anemia.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156235 | PMC |
| http://dx.doi.org/10.7554/eLife.54128 | DOI Listing |
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