“…Additionally, Z-DNA binding proteins, although rare, are involved in gene regulation (Oh et al, 2002), viral pathogenesis (e.g., E3L) (Kim et al, 2003;Kwon and Rich, 2005), innate immune sensing (e.g., ZBP1) (Kuriakose and Kanneganti, 2018;Newton et al, 2016), DNA recognition (e.g., ADAR-1) (Kim et al, 2000), and inflammation (Szczesny et al, 2018). There is also ample experimental evidence of Z-DNA formation in the presence of high ionic strength (Ali and Ali, 1997;Peck et al, 1982), Z-DNA binding proteins (Bae et al, 2011), negative supercoiling (Nordheim et al, 1982;Nordheim and Rich, 1983;Wittig et al, 1991), as well as induction of Z-DNA via nucleotide modification (e.g., methylation and or bromination) that can reduce the high energy activation barrier (Temiz et al, 2012). Although there are Z-prone DNA sequences (e.g., alternating dGdC) (Mo ¨ller et al, 1982), all sequences of DNA are capable of conversion to the Z-form (Kypr et al, 2009).…”