ATR and telangiectasis: The tyrosyl-DNA phosphodiesterase 2 (TDP2) [10], and more recently reported DNA topoisomerases [28] as well as ataxia telangiectasia mutated pathway and Rad3-related pathway and signaling factor CHK1 (ATR-CHK1) [29], which were shown to take part in the synthesis of HBV cccDNA, may serve as examples.