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SUMO ylation promotes protective responses to DNA ‐protein crosslinks
Author(s) -
Borgermann Nikoline,
Ackermann Leena,
Schwertman Petra,
Hendriks Ivo A,
Thijssen Karen,
Liu Julio CY,
Lans Hannes,
Nielsen Michael L,
Mailand Niels
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019101496
Subject(s) - biology , dna , dna binding protein , microbiology and biotechnology , biochemistry , transcription factor , gene
DNA ‐protein crosslinks ( DPC s) 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 DPC s remain incompletely understood. Recent studies unveiled a dedicated DPC repair pathway in higher eukaryotes involving the SprT‐type metalloprotease SPRTN / DVC 1, which proteolytically processes DPC s during DNA replication in a ubiquitin‐regulated manner. Here, we show that chemically induced and defined enzymatic DPC s trigger potent chromatin SUMO ylation responses targeting the crosslinked proteins and associated factors. Consequently, inhibiting SUMO ylation 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 SUMO ylation in promoting germ cell and embryonic survival upon DPC formation. Our findings provide first global insights into signaling responses to DPC s and reveal an evolutionarily conserved function of SUMO ylation in facilitating responses to these lesions in metazoans that may complement replication‐coupled DPC resolution processes.