| Autor: |
Anoop Singh Chauhan, Alexander J. Garvin, Mohammed Jamshad, Joanna R. Morris |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.03.22.485326 |
| Popis: |
The E3 ubiquitin ligase RNF168 is a rate-limiting component of DNA double-strand break signalling that acts to amplify histone ubiquitylation. The confining of RNF168 chromatin spreading around DNA break sites has been related to constraining its expression levels and to the removal of ubiquitin-conjugates to which it binds. Here we identify a new mechanism that suppresses RNF168 amplification at chromatin. We show that depletion of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) or mutation of the Pin1-binding site of RNF168 increases DNA-damage site accumulation of RNF168 to supraphysiological levels without impacting RNF168 expression levels. Pin1 promotes SUMOylation of RNF168 by SUMO2/3, and a SUMO conjugation site on RNF168 is required to restrict RNF168 accumulations. We find Pin1-SUMO mediated-regulation of RNF168 is associated with cellular radioresistance. These data demonstrate that the regulation of chromatin ubiquitylation is actively suppressed by modification of RNF168 to counteract excessive RNF168-ubiquitin spreading. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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