PXD053595

PXD053595 is an original dataset announced via ProteomeXchange.

Title	SART3 promotes homologous recombination repair by stimulating DNA–RNA hybrids removal and DNA end resection
Description	DNA–RNA hybrids triggered by double-strand breaks (DSBs) are crucial intermediates during DSB repair, and their timely resolution requires numbers of RNA helicases, including DEAD box 1 (DDX1). However, how these helicases are recruited to DSB-induced hybrids in time remains largely unclear. Here, we revealed that squamous cell carcinoma antigen recognized by T cells 3 (SART3) promotes DDX1 binding to DNA–RNA hybrids at DSBs for optimal homologous recombination (HR) repair. SART3 itself can associate with DNA–RNA hybrids and PAR chains, and is recruited to DSBs in both PARylation- and hybrid-dependent fashion. SART3 also associates with DDX1 and is necessary for DDX1 enrichment at DSBs. The defective SART3-DDX1 association observed in cells expressing the cancer-associated variant SART3-R836W not only abrogates the accumulation of DDX1 at DSBs, but also impairs hybrid removal and HR efficiency, leading to hypersensitivity of tumor cells to drug treatments. Interestingly, beyond impairing hybrid removal through DDX1, SART3 loss also inhibits DNA end resection, causing a more profound DSB repair defect and chemosensitivity. The stimulatory role of SART3 in end resection is mediated by its function to enhance USP15-BARD1 association and BRCA1-BARD1 retention. Together, our study reveals a previously unknown role of SART3 in DSB repair, rendering SART3 a promising target for cancer therapy.
HostingRepository	PRIDE
AnnounceDate	2025-01-30
AnnouncementXML	Submission_2025-01-30_06:12:26.103.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	慧 傅
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-03 02:01:40	ID requested
⏵ 1	2025-01-30 06:12:26	announced

Dataset with its publication pending

submitter keyword: SART3,homologous recombination repair,DNA–RNA hybrids

Caixia Guo
contact affiliation	Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, China
contact email	guocx@big.ac.cn
lab head
慧 傅
contact affiliation	University of Chinese Academy of Sciences
contact email	fuhui2018m@big.ac.cn
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/2025/01/PXD053595

PRIDE project URI

• PRIDE
  1. PXD053595
     1. Label: PRIDE project
     2. Name: SART3 promotes homologous recombination repair by stimulating DNA–RNA hybrids removal and DNA end resection