PXD058192

PXD058192 is an original dataset announced via ProteomeXchange.

Title	LRRC59 cooperates with nuclear transporters to restrain the nuclear envelope repair machinery and safeguard genome integrity
Description	Nuclear envelope (NE) ruptures in primary nuclei and micronuclei are a hallmark of cancer and persistent ruptures drive cancer-associated genome instability and inflammatory signaling. NE repair relies on the activation of the ESCRT-III machinery by the LEMD2-CHMP7 compartmentalization sensor, but very little is known about the repair processes beyond these core factors. In this study, we used convergent proximity proteomics centered on the LEMD2-CHMP7 node to generate the first NE rupture proteomics inventory. Within this NE repairome, we identified LRRC59 as a critical regulator of LEMD2 and CHMP7 accumulation at sites of NE ruptures. We found that assembly of LEMD2-CHMP7 complexes is controlled by LRRC59 and the importin KPNB1, in synergy with the exportin XPO1. Disruption of this novel regulatory axis escalated spreading of LEMD2 and CHMP7 across the NE, driving the accumulation of DNA torsional stress and DNA damage in ruptured primary nuclei and micronuclei. Taken together, our work provides a molecular inventory for studying nuclear integrity and identifies a novel layer of regulation of NE repair centered on LRRC59. We propose that dysregulation of LRRC59 and altered nuclear import/export in cancer cells coordinately perturbs NE repair, driving genome instability and cancer development.
HostingRepository	PRIDE
AnnounceDate	2025-12-12
AnnouncementXML	Submission_2025-12-12_08:51:29.064.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tuula Nyman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-23 03:31:35	ID requested
⏵ 1	2025-12-12 08:51:29	announced

10.1038/S41467-025-65994-4;

submitter keyword: Nucleus, Nuclear envelope rupture, Genome Stability, ESCRT-III, Cancer, Micronuclei

Tuula Nyman
contact affiliation	Head of Proteomics
contact email	tuula.nyman@medisin.uio.no
lab head
Tuula Nyman
contact affiliation	University of Oslo
contact email	tuula.nyman@medisin.uio.no
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/2025/12/PXD058192

PRIDE project URI

• PRIDE
  1. PXD058192
     1. Label: PRIDE project
     2. Name: LRRC59 cooperates with nuclear transporters to restrain the nuclear envelope repair machinery and safeguard genome integrity