Given that the yeast PKA catalytic subunits (Tpk1-3) share 47–49% sequence identity with their human PRKACB counterpart (3e–127 ≤ E-value ≤ 7e–121; Supplementary Figure S3C), and the yeast Nej1 human homolog, XLF, facilitates NHEJ by bringing together broken DSB ends (34), we examined whether PRKACB and XLF display similar NHEJ activity in human U2OS osteosarcoma cells (an in vitro model cell line for studying DDR genes (20)). Here, NHEJ1 is linked to osteosarcoma.