PXD066473-1

PXD066473 is an original dataset announced via ProteomeXchange.

Title	Nuclear Phosphatidylinositol 3-Phosphate Produced by Beclin-1/Vps34 Directly Orchestrates DNA Mismatch Repair
Description	DNA mismatch repair (MMR) is essential for maintaining genome integrity, yet its regulation by non-protein biomolecules remains poorly understood. Here, we uncover nuclear phosphatidylinositol 3-phosphate (PI3P) as a previously unrecognized lipid mediator of MMR. PI3P, canonically produced by the Beclin-1/Vps34 complex in the cytoplasm, is also synthesized within the nucleus, where it plays a direct and functionally critical role in orchestrating MMR. Nuclear PI3P physically associates with core MMR proteins and facilitates the assembly of MutSα and MutSβ complexes, enabling mismatch recognition and subsequent repair. Inhibition of Beclin-1 or Vps34 compromises nuclear PI3P production, which impairs MMR recognition complex formation, leading to microsatellite instability. Conversely, supplementation with exogenous PI3P restores MMR recognition complex assembly and mismatched substrate binding in vitro, confirming its functional necessity. Our study reveals a noncanonical, autophagy-independent function of the nuclear Beclin-1/Vps34 complex in genome surveillance, and identifies nuclear phospholipids as versatile regulators of DNA repair.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-06_16:13:02.369.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Robin Antrobus
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-23 08:06:38	ID requested
⏵ 1	2026-09-06 16:13:03	announced

10.1093/nar/gkag696;

Li X, Vicinanza M, Lopez A, Festa BP, Schlotawa L, Barbosa AD, Takla M, Balmus G, Fleming A, Rubinsztein DC, Nuclear PI3P produced by the Beclin-1/Vps34 complex regulates DNA mismatch repair. Nucleic Acids Res, 54(13):(2026) [pubmed]

submitter keyword: autophagy,IP-MS, DNA mismatch repair, genome stability

Prof. David C. Rubinsztein
contact affiliation	Cambridge Institute for Medical Research (CIMR), Department of Genomic Medicine, University of Cambridge, Cambridge CB2 0XY
contact email	dcr1000@cam.ac.uk
lab head
Robin Antrobus
contact affiliation	CIMR medicine
contact email	pra29@cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066473
     1. Label: PRIDE project
     2. Name: Nuclear Phosphatidylinositol 3-Phosphate Produced by Beclin-1/Vps34 Directly Orchestrates DNA Mismatch Repair