PXD063287-1

PXD063287 is an original dataset announced via ProteomeXchange.

Title	miRNA-mediated cell-to-cell communications boost DNA repair during the Radioadaptative Response in human fibroblasts
Description	The radioadaptive response is a phenomenon in which cells exposed to a low priming dose of ionizing radiation develop increased resistance for a period of time to a subsequent higher challenging dose. Little is known of the molecular components of this response. Here, we focus on determining if during the RAR there are changes in the Homologous Recombination, the more faithful DNA Double Strand break repair pathway. Using immortalized fibroblasts as a model system, we demonstrate that primed cells exhibit faster DNA resection, the initial step of homologous recombination, following a challenging dose, as indicated by RPA foci kinetics. We further establish that the stimulation of resection during the RAR is mostly established and maintained through a bystander effect mediated by cell-to-cell communication via extracellular vesicles. Indeed, media exchange experiments demonstrated that soluble factors in the conditioned media were sufficient to fully recapitulate the RAR effect. RNA analyses of extracellular vesicles cargo revealed differential expression of miRNAs, particularly miR-126-3p and miR-451a, which we show play crucial roles in modulating the RAR. Notably, inhibition of miR-451a was sufficient to induce the RAR in cells that typically do not exhibit this response. Finally, we identified the p38-CCAR2 axis as a critical regulator of the RAR-mediated DNA end resection boost. p38 activation following priming irradiation block CCAR2 activity, facilitating a more efficient repair process. Collectively, our findings elucidate a novel mechanism by which EV-mediated communication and specific miRNA signaling enhance HR efficiency in response to radiation, offering insights into potential therapeutic applications in radiotherapy.
HostingRepository	PRIDE
AnnounceDate	2026-08-03
AnnouncementXML	Submission_2026-08-03_14:41:08.738.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Román González-Prieto
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF SCP

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-24 07:56:00	ID requested
⏵ 1	2026-08-03 14:41:09	announced

10.1093/NAR/GKAG764;

submitter keyword: Radioadaptative response/bystander effect/DNA end resection/DNA repair

Román González-Prieto
contact affiliation	CABIMER, ES
contact email	roman.gonzalez@cabimer.es
lab head
Román González-Prieto
contact affiliation	Andalusian Center for Regenerative Medicine and Cell Biology, CABIMER, University of Seville
contact email	roman.gonzalez@cabimer.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063287
     1. Label: PRIDE project
     2. Name: miRNA-mediated cell-to-cell communications boost DNA repair during the Radioadaptative Response in human fibroblasts