PXD033739-2

PXD033739 is an original dataset announced via ProteomeXchange.

Title	The SUMO-NIP45 pathway guards against accumulation of toxic DNA catenanes
Description	SUMOylation 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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:02:54.916.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	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-06 04:07:15	ID requested
1	2023-07-21 04:48:13	announced
⏵ 2	2023-11-14 09:02:55	announced	2023-11-14: Updated project metadata.
3	2024-10-22 05:57:19	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: BTRR,SUMO, SUMOylation, PICH, human, DNA catenane, DNA damage, SLX4, NIP45

Michael Lund Nielsen
contact affiliation	Proteomics program, 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	Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
contact email	ivo.a.hendriks@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/07/PXD033739

PRIDE project URI

• PRIDE
  1. PXD033739
     1. Label: PRIDE project
     2. Name: The SUMO-NIP45 pathway guards against accumulation of toxic DNA catenanes