X-ray repair cross-complementing protein 5 (XRCC5) (XRCC5)

X-ray repair cross-complementing protein 5 (XRCC5), commonly known as Ku80, is a critical component of the non-homologous end joining (NHEJ) pathway, the primary mechanism for repairing DNA double-strand breaks in mammalian cells [1]. It forms a heterodimer with XRCC6 (Ku70) to bind DNA ends and recruit the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) [2]. In the context of oncology, XRCC5 is frequently overexpressed in various tumors, where it contributes to therapeutic resistance by efficiently repairing DNA damage induced by ionizing radiation and certain chemotherapeutic agents [3]. Targeting XRCC5 mRNA or the protein itself is an active area of research aimed at sensitizing cancer cells to DNA-damaging treatments [4]. However, because XRCC5 is also essential for V(D)J recombination in the immune system and general genomic stability, therapeutic strategies must carefully manage potential off-target effects and systemic toxicity [5]. [1] UniProt P13010 (XRCC5_HUMAN). [2] PubMed: 15573114 (Ku70/Ku80 function). [3] PubMed: 28651543 (XRCC5 in cancer resistance). [4] PubMed: 31484080 (Targeting Ku80 for radiosensitization). [5] PubMed: 11017136 (Ku80 and V(D)J recombination).

Other names

Ku80Ku86KUB2NFIVG22P2Lupus Ku autoantigen protein p80ATP-dependent DNA helicase II 80 kDa subunit

Inhibition of the non-homologous end joining (NHEJ) pathway by preventing the formation or function of the Ku70/Ku80 heterodimer, thereby sensitizing cells to DNA-damaging agents.