In addition, 5hmdC exposure promoted FANCD2 monoubiquitylation in human eHAP and chicken DT40 cell lines in a dose-dependent manner (Supplementary Fig. 2B), indicating that 5hmdC was taken by cells, activated FANCD2 monoubiquitylation and induced chromosomal instability and lethality in FA cell lines, and suggest that the cytosine demethylation nucleoside 5hmdC elicits a classical DNA damage response in FA cells, unveiling a novel role of the FA pathway in maintaining genome integrity and survival. The gene discussed is FANCA; the disease is Friedreich ataxia.