PXD062583-1

PXD062583 is an original dataset announced via ProteomeXchange.

Title	ER-tethering directs TREX1 penetration of a BAF-dependent barrier at micronuclei
Description	Micronuclei are membrane-encapsulated nuclear aberrations that form following cell division errors. Micronuclear membrane collapse results in DNA damage and cGAS-STING activation. TREX1 inhibits cGAS activation by degrading micronuclear DNA. Aside from a dependency on ER-tethering, the mechanisms directing TREX1 activity at micronuclei are unknown. Here, we identify BAF as a key regulator of TREX1 activity at micronuclei. BAF accumulates on micronuclei following membrane collapse and recruits TREX1 in a mechanism that depends on BAF interactions with LEM-domain proteins. Unexpectedly, despite delayed recruitment, TREX1 exhibits enhanced micronuclear DNA degradation and functions independently of the ER in BAF-deficient cells. Mechanistically, high concentrations of BAF inhibit TREX1-mediated DNA degradation in vitro in a manner that depends on BAF DNA-binding ability. BAF similarly outcompetes cGAS for micronuclear DNA and suppresses cGAS activation at micronuclei. Thus, ER-tethering allows TREX1 to selectively penetrate a BAF-dependent protective barrier at ruptured micronuclei that limits innate immunity in chromosomally unstable cells.
HostingRepository	PRIDE
AnnounceDate	2026-03-09
AnnouncementXML	Submission_2026-03-09_13:23:52.482.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex Kentsis
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-03 13:12:44	ID requested
⏵ 1	2026-03-09 13:23:52	announced

Dataset with its publication pending

submitter keyword: chromosomal instability, micronuclei, STING, chromothripsis,TREX1, cGAS

Alex Kentsis
contact affiliation	Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
contact email	kentsisresearchgroup@gmail.com
lab head
Alex Kentsis
contact affiliation	Memorial Sloan Kettering Cancer Center
contact email	kentsisresearchgroup@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062583
     1. Label: PRIDE project
     2. Name: ER-tethering directs TREX1 penetration of a BAF-dependent barrier at micronuclei