Small-Molecule Inhibition of UBE2T/FANCL-Mediated Ubiquitylation in the Fanconi Anemia Pathway.

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ID: 51452
2019
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Abstract
The Fanconi anemia pathway orchestrates the repair of DNA interstrand cross-links and stalled replication forks. A key step in this pathway is UBE2T and FANCL-dependent monoubiquitylation of the FANCD2-FANCI complex. The Fanconi anemia pathway represents an attractive therapeutic target, because activation of this pathway has been linked to chemotherapy resistance in several cancers. However, to date, very few selective inhibitors of ubiquitin conjugation pathways are known. By using a high-throughput screen-compatible assay, we have identified a small-molecule inhibitor of UBE2T/FANCL-mediated FANCD2 monoubiquitylation that sensitizes cells to the DNA cross-linking agent, carboplatin.
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cornwell2019smallmoleculeacs Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Cornwell, Matthew J;Thomson, Graeme J;Coates, Julia;Belotserkovskaya, Rimma;Waddell, Ian D;Jackson, Stephen P;Galanty, Yaron;
Journal ACS chemical biology
Year 2019
DOI
10.1021/acschembio.9b00570
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