ATR and myalgic encephalomeyelitis/chronic fatigue syndrome: One of the most compelling evidence lines that replication is perturbed at CFS and that correct handling of perturbed forks is important for CFS stability is provided by the observation that genetic downregulation of ATR, the upstream S-phase checkpoint kinase [35, 36], dramatically and specifically, affects fragility of CFS, even in the absence of aphidicolin [37].