XRCC3

XRCC3, or X-ray repair cross-complementing protein 3, is a human gene encoding a member of the RAD51 family of recombinase-like proteins that participate in the homologous recombination repair of DNA double-strand breaks. The XRCC3 protein supports accurate repair by homologous recombination, particularly after replication stress or exposure to ionizing radiation.

XRCC3 operates within the RAD51 paralog network and interacts with RAD51 and other RAD51 paralogs. In humans, it participates in two paralogous complexes: the XRCC2-XRCC3 complex and the RAD51B-RAD51C-RAD51D complex, which cooperate to promote RAD51 filament formation and strand invasion during repair of double-strand breaks.

Deficiency or loss of XRCC3 leads to genomic instability and increased cellular sensitivity to DNA damaging agents, reflecting its role in maintaining genome integrity. The protein is primarily localized in the nucleus and is expressed across many tissues.

Genetic variation in XRCC3 has been examined for cancer susceptibility. A common coding polymorphism, Thr241Met (rs861539), has been studied in relation to risk for several cancers, including breast, lung, and ovarian cancer, but findings are inconsistent and do not establish a clear effect. Rare variants or altered expression may influence DNA repair capacity and responses to radiotherapy.

Overall, XRCC3 is a conserved component of the homologous recombination machinery that contributes to genomic stability and the cellular response to DNA damage.