PER2 and osteosarcoma: To create knock-in U-2 OS cells (a human osteosarcoma cell line, which is widely used as a model cell line in the circadian field40–44, see also Supplementary Note 3) expressing PER2 or CRY1 C-terminally fused to fluorescence proteins from their endogenous promoters, we transfected U-2 OS wild-type cells with spCas9/sgRNA expression plasmid(s), the donor plasmid, and a plasmid expressing an inhibitor of the p53-binding protein, which enhances HDR efficiency by suppressing NHEJ45 (Fig. 1b).