SUMOylation promotes protective responses to DNA-protein crosslinks
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SUMOylation promotes protective responses to DNA-protein crosslinks. / Borgermann, Nikoline; Ackermann, Leena; Schwertman, Petra; Hendriks, Ivo A; Thijssen, Karen; Liu, Julio Cy; Lans, Hannes; Nielsen, Michael L; Mailand, Niels.
In: E M B O Journal, Vol. 38, e101496, 2019.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - SUMOylation promotes protective responses to DNA-protein crosslinks
AU - Borgermann, Nikoline
AU - Ackermann, Leena
AU - Schwertman, Petra
AU - Hendriks, Ivo A
AU - Thijssen, Karen
AU - Liu, Julio Cy
AU - Lans, Hannes
AU - Nielsen, Michael L
AU - Mailand, Niels
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
U2 - 10.15252/embj.2019101496
DO - 10.15252/embj.2019101496
M3 - Journal article
C2 - 30914427
VL - 38
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
M1 - e101496
ER -
ID: 216015963