PXD047189

PXD047189 is an original dataset announced via ProteomeXchange.

Title	Retinoic acid-induced 2 protein contributes to proficient homologous recombination and maintains genomic stability in breast cancer
Description	Genome instability is a fundamental feature and hallmark of cancer associated with aggressiveness, drug resistance and poor prognosis. Here, we provide evidence for an essential function of the Retinoic acid-induced 2 (RAI2) protein as a suppressor of genome instability. Analysis of clinical samples revealed that in primary breast tumors, low RAI2 gene expression is significantly associated with genomically unstable tumors and poor prognosis. RAI2 depletion in breast cancer cell lines resulted in loss of mitotic fidelity characterized by prolonged mitosis with increased chromosome segregation errors and micronuclei formation. Drug screening revealed increased sensitivity of RAI2-depleted breast cancer cells to topoisomerase I and Aurora A inhibitors. We also found that genotoxic stress induces RAI2 protein, which shows affinity for poly-(ADP-ribose) and contributes to efficient DNA repair by homologous recombination. We validated the functional association of RAI2 gene expression with DNA double-strand break repair capacity in clinical samples. Our findings support, for the first time, an important functional role of RAI2 in the maintenance of mitotic fidelity and DNA repair associated with early metastatic relapse.
HostingRepository	PRIDE
AnnounceDate	2025-08-04
AnnouncementXML	Submission_2025-08-03_16:27:33.686.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Mair
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C labeled residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-23 03:13:21	ID requested
⏵ 1	2025-08-03 16:27:34	announced

10.1186/s13058-025-02085-8;

Boettcher L, Greimeier S, Borgmann K, Mughal SS, Ellinger B, Bartkowiak K, Zobiak B, Failla AV, Steffen P, Claus E, Besler K, Buccitelli C, Schaaf V, Ozga AK, Parretta S, Schneegans S, Mansour WY, Korbel JO, Schlueter H, Brors B, Pantel K, Wikman H, Werner S, Retinoic acid-induced 2 deficiency impairs genomic stability in breast cancer. Breast Cancer Res, 27(1):137(2025) [pubmed]

submitter keyword: genomic instability, premature mitotic entry,breast cancer, homologous recombination, poly-(ADP-ribose)

Stefan Werner
contact affiliation	Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf Martinistraße 52, 20246 Hamburg, Germany
contact email	st.werner@uke.de
lab head
Thomas Mair
contact affiliation	Section for Mass Spectrometry and Proteomics, University Medical Center Hamburg-Eppendorf
contact email	t.mair@uke.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047189
     1. Label: PRIDE project
     2. Name: Retinoic acid-induced 2 protein contributes to proficient homologous recombination and maintains genomic stability in breast cancer