Genotoxic stress caused by carcinogens like Cigarette smoke activate both the MAPK pathway and the S phase checkpoint in Schizosaccharomyces pombe. But the cross talk between these two pathways has not been investigated in great detail in fission yeast. This study deals with the molecular mechanism of co-ordination between the two regulatory pathways. We show that both the pathways have a common effector molecule, namely Cdc25, the cell cycle regulatory phosphatase. We demonstrate that the MAPK Sty1 interacts with Cdc25 and prevents mitotic entry in S. pombe cells exposed to CSE. To our knowledge, this is the first demonstration of interaction between Sty1 and Cdc25 in S. pombe. The functional significance of this interaction lies in effecting Cdc25 turnover after CSE exposure in S. pombe. We show that Cdc25 turnover after CSE treatment is dependent on the presence of Rad3 activity and Sty1-Cdc25 interaction. Our study suggests that the Cigarette Smoke Extract (CSE) induced stress is counteracted by the simultaneous activation of a mitotic checkpoint in addition to the previously described S phase checkpoint. We also show that Sty1 activity is not essential for activation of the S phase checkpoint. ©2008 Landes Bioscience.