Abhimanu Pandey, Cheng Shen, Shouya Feng, Daniel Enosi Tuipulotu, Chinh Ngo, Cheng Liu, Melan Kurera, Anukriti Mathur, Shweta Venkataraman, Jing Zhang, Dipti Talaulikar, Renhua Song, Justin J-L Wong, Narci Teoh, Nadeem O Kaakoush, Si Ming Man
The innate immune response contributes to the development or attenuation of acute and chronic diseases, including cancer. Microbial DNA and mislocalized DNA from damaged host cells can activate different host responses that shape disease outcomes. Here, we show that mice and humans lacking a single allele of the DNA repair protein Ku70 had increased susceptibility to the development of intestinal cancer. Mechanistically, Ku70 translocates from the nucleus into the cytoplasm where it binds to cytosolic DNA and interacts with the GTPase Ras and the kinase Raf, forming a tripartite protein complex and docking at Rab5+ Rab7+ early-late endosomes...
January 26, 2024: Science Advances