X-ray repair cross-complementing protein 6 (Ku70) (Ku70)

X-ray repair cross-complementing protein 6, commonly known as Ku70, is a pivotal DNA-binding protein that forms a heterodimer with Ku80 to initiate the non-homologous end joining (NHEJ) pathway, the primary mechanism for repairing DNA double-strand breaks in mammalian cells [1, 11]. The Ku70/80 complex functions as a molecular scaffold that rapidly recognizes and binds to broken DNA ends, subsequently recruiting the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and other repair factors [2, 14]. Beyond its central role in maintaining genomic integrity, Ku70 is involved in telomere protection, Bax-mediated apoptosis, and acts as a cytosolic DNA sensor that triggers innate immune responses [4, 5]. In the context of oncology, Ku70 is often upregulated in various tumors, where it contributes to therapeutic resistance by efficiently repairing damage caused by ionizing radiation and chemotherapeutic agents [7, 15]. This has led to the development of small-molecule inhibitors, such as STL127705 and UMI-77, which aim to disrupt Ku-DNA interactions and sensitize cancer cells to DNA-damaging therapies [23, 29]. However, therapeutic targeting of Ku70 is complicated by its essential role in normal cell survival and its requirement for V(D)J recombination during immune system development [16, 27]. Additionally, Ku70 is a known autoantigen in systemic autoimmune diseases like lupus and polymyositis, further highlighting its complex biological significance [1, 11].

Other names

XRCC6G22P1Lupus Ku autoantigen protein p70ATP-dependent DNA helicase 2 subunit 1CTC75CTCBFML8TLAA

Inhibition of Ku-DNA binding and disruption of the Ku70/80 heterodimer to block non-homologous end joining (NHEJ) and sensitize cells to DNA-damaging agents.