PXD068465

PXD068465 is an original dataset announced via ProteomeXchange.

Title	GNL3 SUMOylation is essential for DNA double-strand break repair by homologous recombination
Description	DNA double-strand break (DSB) repair via homologous recombination (HR) is critical for maintaining genomic integrity and requires proper DNA end resection to generate ssDNA overhangs. Yet, how this critical step is regulated in cells remains to be understood. Here, we report that GNL3, a nucleolar GTP-binding protein, plays a critical role in HR repair via regulating DNA end resection dependently on its SUMOylation. Ectopic expression of wild-type, but not the SUMO-defective K196R mutant, GNL3 completely abolished DNA damage response induced by knockdown of endogenous GNL3. GNL3 interacts with the BLM-DNA2 helicase-nuclease complex and is critical for DNA end resection and subsequent RPA and RAD51 loading. The GNL3-BLM interaction requires SUMOylation and SUMO-interacting motifs (SIMs) of both proteins. We further showed that USP36, a nucleolar deubiquitinating enzyme, acts as a novel SUMO ligase for GNL3, whereas SUMOylated GNL3 can be deSUMOylated by the SUMO protease SENP3. Interestingly, several breast cancer-derived variants of GNL3 that interfere with its SUMOylation of SIM failed to interact with the BLM-DNA2 complex. Knockdown of GNL3 sensitizes breast cancer cells to the treatment with etoposide or Olaparib. Together, our results reveal that GNL3 SUMOylation is critical for HR repair and targeting GNL3 SUMOylation may induce HR deficiency and sensitize breast cancers to DNA damage-inducing agents.
HostingRepository	PRIDE
AnnounceDate	2026-06-16
AnnouncementXML	Submission_2026-06-16_13:54:37.244.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Wilmarth
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-17 14:02:54	ID requested
⏵ 1	2026-06-16 13:54:37	announced

Dataset with its publication pending

submitter keyword: breast cancer, mass spectrometry,Homologous recombination, GNL3 SUMOylation, quantitative proteomics

Mu-Shui Dai
contact affiliation	Department of Molecular & Medical Genetics, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
contact email	daim@ohsu.edu
lab head
Phillip Wilmarth
contact affiliation	OHSU
contact email	wilmarth@ohsu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD068465
     1. Label: PRIDE project
     2. Name: GNL3 SUMOylation is essential for DNA double-strand break repair by homologous recombination