The fungal pathogen Setosphaeria turcica causes northern corn leaf blight (NCLB), which leads to considerable crop losses.  Setosphaeria turcica elaborates a specialized infection structures called appressorium for maize infection.  Previously, we demonstrated that the S. turcica triggers an S-phase checkpoint and ATR (Ataxia Telangiectasia and Rad3 related)-dependent self-protective response to DNA genotoxic insults during maize infection.  However, how the regulatory mechanism works was still largely unknown.  Here, we report a genome wide transcriptional profile analysis during appressorium formation in the present of DNA replication stress.  We performed RNA-Seq analysis to identify S. tuicica genes responsive to DNA replication stress.  In the current work, we found that appressorium-mediated maize infection by S. turcica is significantly blocked by S-phase checkpoint.  A large serial of secondary metabolite and melanin biosynthesis genes were blocked in appressorium formation of S. turcica during the replication stress.  The secondary metabolite biosynthesis genes including alcohol dehydrogenase GroES-like domain, multicopper oxidase, ABC-transporter families, cytochrome P450 and FAD-containing monooxygenase were related to plant pathogen infection.  In addition, we demonstrated that autophagy in S. turcica is up-regulated by ATR as a defense response to stress.  We identified StATG3, StATG4, StATG5, StATG7 and StATG16 genes for autophagy were induced by ATR-mediated S-phase checkpoint.  We therefore propose that in response to genotoxic stress, S. turcica utilizes ATR-dependent pathway to turn off transcription of genes governing appressorium-mediated infection, and meanwhile inducing transcription of autophagy genes likely as a mechanism of self-protection, aside from the more conservative responses in eukaryotes.