Apart from the well-established functions in resolving the DNA interstrand crosslinks, roles of the FA pathway preserving CFS stability and mitigating the R-loop-associated genome instability is growingly appreciated [16–20, 50, 51]; in particular, FANCD2 localizes to sites of transcription [20], and purified FANCD2-FANCI heterodimer can directly bind to R-loops [17, 18]. This evidence concerns the gene FANCD2 and myalgic encephalomeyelitis/chronic fatigue syndrome.