PXD009040

PXD009040 is an original dataset announced via ProteomeXchange.

Title	A SUMO-mediated protective response to DNA-protein crosslinks
Description	DNA-protein crosslinks (DPCs) are highly cytotoxic lesions that obstruct essential DNA transactions and whose resolution is critical for cell and organismal fitness. However, unlike the repair pathways for most types of DNA damage, the mechanisms by which cells respond to and overcome DPCs remain poorly 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-controlled manner. Here, we show that aldehyde-generated DPCs elicit a potent and highly dynamic, cell cycle-independent SUMOylation response impacting numerous chromatin-associated human proteins. We identify an uncharacterized SprT metalloprotease, ACRC, which unlike SPRTN is targeted to DPCs in a SUMO-dependent manner. Moreover, we establish important physiological roles of the C. elegans ACRC orthologue GCNA-1 and SUMO-mediated signaling in promoting organismal survival upon DPC formation. Finally, we demonstrate that like aldehydes, defined enzymatic DNMT1 DPCs trigger a robust SUMO response targeting the crosslinked proteins and associated factors to promote efficient lesion processing and cellular fitness. Collectively, our findings reveal an evolutionarily conserved general role of SUMO-mediated signaling in facilitating responses to DPCs in metazoans.
HostingRepository	PRIDE
AnnounceDate	2019-03-26
AnnouncementXML	Submission_2019-03-28_13:46:33.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ivo Hendriks
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	sumoylated lysine
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2018-02-26 07:08:24	ID requested
1	2019-03-26 08:27:47	announced
⏵ 2	2019-03-28 13:46:34	announced	Updated publication reference for PubMed record(s): 30914427.

Borgermann N, Ackermann L, Schwertman P, Hendriks IA, Thijssen K, Liu JC, Lans H, Nielsen ML, Mailand N, SUMOylation promotes protective responses to DNA-protein crosslinks. EMBO J, 38(8):(2019) [pubmed]

curator keyword: Biological

submitter keyword: SUMO, ubquitin, DNMT1, DNA-protein crosslink, DNA damage, DNA repair, human, Q Exactive HF, Q Exactive HF-X

Michael Lund Nielsen
contact affiliation	Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact email	michael.lund.nielsen@cpr.ku.dk
lab head
Ivo Hendriks
contact affiliation	Novo Nordisk Foundation Center for Protein Research, University of Copenhagen
contact email	ivo.a.hendriks@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009040
     1. Label: PRIDE project
     2. Name: A SUMO-mediated protective response to DNA-protein crosslinks