The current model of FA/BRCA pathway activation, based on studies in U2OS osteosarcoma cells, DT40 chicken B cells and in vitro assays, links ATR to downstream FANCD2 monoubiquitination through the phosphorylation of FANCI, a FANCD2 paralog, in the presence of catastrophic interstrand crosslinking damage or long-term treatment with HU (48,50,54). Here, FANCD2 is linked to osteosarcoma.