Retinoic acid-induced 2 protein contributes to proficient homologous recombination and maintains genomic stability in breast cancer

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Thomas Mair  

LAB HEAD: Stefan Werner

PROVIDER: PXD047189 | Pride | 2025-08-04

REPOSITORIES: Pride