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PXD033739

PXD033739 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe SUMO-NIP45 pathway guards against accumulation of toxic DNA catenanes
DescriptionSUMOylation is an essential protein modification that regulates numerous biological processes, but what constitutes its most critical functions in the cell remains unclear. Here, using genome-scale CRISPR-Cas9-based synthetic lethality screens, we show that the BLM-TOP3A-RMI1-RMI2 (BTRR)-PICH pathway, which resolves ultra-fine anaphase DNA bridges (UFBs) arising from catenated DNA structures, and NIP45 (NFATC2IP) display a synthetic lethal interaction in human cells and are essential for proliferation when SUMOylation is impaired. NIP45 and SUMOylation prevent excessive UFB formation that leads to extensive binucleation when BTRR-PICH-dependent UFB resolution is defective, by orchestrating an interphase pathway for converting DNA catenanes into DNA double-strand breaks that trigger G2 arrest via canonical ATM/ATR-dependent DNA damage signaling. NIP45 exerts its crucial function in this pathway by acting as a cofactor for specific SUMOylation processes that are at least in part targeted to the SLX4 multi-nuclease complex, which may facilitate nucleolytic DNA catenane resolution. Our findings establish an essential role of SUMO signaling in underpinning cell proliferation by counteracting the deleterious threat to faithful chromosome segregation posed by toxic DNA catenanes arising in virtually every cell cycle, via non-epistatic NIP45- and BTRR-PICH-dependent pathways.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:57:19.093.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterIvo Hendriks
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-05-06 04:07:15ID requested
12023-07-21 04:48:13announced
22023-11-14 09:02:55announced2023-11-14: Updated project metadata.
32024-10-22 05:57:19announced2024-10-22: Updated project metadata.
Publication List
10.1038/S41594-023-01045-0;
Keyword List
submitter keyword: BTRR,SUMO, SUMOylation, PICH, human, DNA catenane, DNA damage, SLX4, NIP45
Contact List
Michael Lund Nielsen
contact affiliationProteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact emailmichael.lund.nielsen@cpr.ku.dk
lab head
Ivo Hendriks
contact affiliationProteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact emailivo.a.hendriks@gmail.com
dataset submitter
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