09 January 2015

New paper on SUMO-dependent regulation of the Fanconi Anemia DNA repair pathway by Mailand Group in Molecular Cell

In this new article in Molecular Cell Novo Nordisk Foundation Center for Protein Research researchers uncover a regulatory role for SUMOylation in the Fanconi Anemia (FA) DNA repair pathway, and propose that ubiquitin-SUMO signaling circuitry is a mechanism that contributes to the balance of activated ID complex dosage at sites of DNA damage.

We show that central components of the Fanconi Anemia (FA) DNA repair pathway, the tumor suppressor proteins FANCI and FANCD2 (the ID complex), are SUMOylated in response to replication fork stalling. The ID complex is SUMOylated in a manner that depends on the ATR kinase, the FA ubiquitin ligase core complex, and the SUMO E3 ligases PIAS1/PIAS4 and is antagonized by the SUMO protease SENP6. SUMOylation of the ID complex drives substrate selectivity by triggering its polyubiquitylation by the SUMO-targeted ubiquitin ligase RNF4 to promote its removal from sites of DNA damage via the DVC1-p97 ubiquitin segregase complex. Deregulation of ID complex SUMOylation compromises cell survival following replication stress. Our results uncover a regulatory role for SUMOylation in the FA pathway, and we propose that ubiquitin-SUMO signaling circuitry is a mechanism that contributes to the balance of activated ID complex dosage at sites of DNA damage.

Read full article: SUMO Circuitry Controls Activated Fanconi Anemia ID Complex Dosage in Response to DNA Damage                                                                                       

Authors from Novo Nordisk Foundation Center for Protein Research:

Ian Gibbs-Seymour
Yasuyoshi Oka
Brian T. Weinert
Jesper V. Olsen
Chunaram Choudhary
Simon Bekker-Jensen
Niels Mailand