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SUMOylation promotes protective responses to DNA‐protein crosslinks

DNA‐protein crosslinks (DPCs) are highly cytotoxic lesions that obstruct essential DNA transactions and whose resolution is critical for cell and organismal fitness. However, the mechanisms by which cells respond to and overcome DPCs remain incompletely understood. Recent studies unveiled a dedicate...

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Detalles Bibliográficos
Autores principales: Borgermann, Nikoline, Ackermann, Leena, Schwertman, Petra, Hendriks, Ivo A, Thijssen, Karen, Liu, Julio CY, Lans, Hannes, Nielsen, Michael L, Mailand, Niels
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463212/
https://www.ncbi.nlm.nih.gov/pubmed/30914427
http://dx.doi.org/10.15252/embj.2019101496
Descripción
Sumario:DNA‐protein crosslinks (DPCs) are highly cytotoxic lesions that obstruct essential DNA transactions and whose resolution is critical for cell and organismal fitness. However, the mechanisms by which cells respond to and overcome DPCs remain incompletely understood. Recent studies unveiled a dedicated DPC repair pathway in higher eukaryotes involving the SprT‐type metalloprotease SPRTN/DVC1, which proteolytically processes DPCs during DNA replication in a ubiquitin‐regulated manner. Here, we show that chemically induced and defined enzymatic DPCs trigger potent chromatin SUMOylation responses targeting the crosslinked proteins and associated factors. Consequently, inhibiting SUMOylation compromises DPC clearance and cellular fitness. We demonstrate that ACRC/GCNA family SprT proteases interact with SUMO and establish important physiological roles of Caenorhabditis elegans GCNA‐1 and SUMOylation in promoting germ cell and embryonic survival upon DPC formation. Our findings provide first global insights into signaling responses to DPCs and reveal an evolutionarily conserved function of SUMOylation in facilitating responses to these lesions in metazoans that may complement replication‐coupled DPC resolution processes.