PXD032143

PXD032143 is an original dataset announced via ProteomeXchange.

Title	Radiation-induced bystander effect mediated by exosomes involves the replication stress in recipient cells.
Description	Exosomes released by irradiated cells mediate radiation-induced bystander effect, which is manifested by DNA breaks detected in recipient cells, yet the specific mechanism responsible for generation of chromosome lesions remains unclear. In this study, naïve FaDu head and neck cancer cells were stimulated with exosomes released by irradiated (a single 2Gy dose) or mock-irradiated cells. Maximum accumulation of gamma H2A.X foci, a marker of DNA breaks, was detected after one hour of stimulation with exosomes from irradiated donors, the level of which was comparable to the one observed in directly irradiated cells (a weaker wave of the gamma H2A.X foci accumulation was also noted after 23 hours of stimulation). Exosomes from irradiated cells, but not from control ones, activated two stress-induced protein kinases: ATM and ATR. Noteworthy, while direct irradiation activated only ATM, both ATM and ATR were activated by two factors known to induce the replication stress: hydroxyurea and camptothecin (with subsequent phosphorylation of gamma H2A.X). One hour of stimulation with exosomes from irradiated cells suppressed DNA synthesis in recipient cells and resulted in the subsequent nuclear accumulation of RNA:DNA hybrids, which is an indicator of impaired replication. Interestingly, the abovementioned effects were observed before a substantial internalization of exosomes, which may suggest a receptor-mediated mechanism. After one hour of stimulation with exosomes from irradiated donors increased phosphorylation of several nuclear proteins was observed, including replication factors and regulators of heterochromatin remodeling, as well as components of multiple intracellular signaling pathways. Hence, we concluded that the bystander effect mediated by exosomes released from irradiated cells involves the replication stress in recipient cells.
HostingRepository	PRIDE
AnnounceDate	2022-05-20
AnnouncementXML	Submission_2022-05-20_08:10:18.099.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Monika Pietrowska
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-09 02:05:36	ID requested
⏵ 1	2022-05-20 08:10:19	announced

Smolarz M, Skoczylas Ł, Gawin M, Krzy, ż, owska M, Pietrowska M, Wid, ł, ak P, Radiation-Induced Bystander Effect Mediated by Exosomes Involves the Replication Stress in Recipient Cells. Int J Mol Sci, 23(8):(2022) [pubmed]

submitter keyword: bystander effect

exosomes

ionizing radiation

non-targeted effects of radiation

replication stress

Piotr Widlak
contact affiliation	Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch
contact email	piotr.widlak@io.gliwice.pl
lab head
Monika Pietrowska
contact affiliation	Maria Sklodowska-Curie National Research Institute of Oncology
contact email	monika.pietrowska@io.gliwice.pl
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/2022/05/PXD032143

PRIDE project URI

• PRIDE
  1. PXD032143
     1. Label: PRIDE project
     2. Name: Radiation-induced bystander effect mediated by exosomes involves the replication stress in recipient cells.