RecQ DNA Helicase Rqh1 Promotes Rad3 ATR  Kinase Signaling in the DNA Replication Checkpoint Pathway of Fission Yeast.
Rad3 is the orthologue of ATR and the sensor kinase of the DNA replication checkpoint in  Schizosaccharomyces pombe  Under replication stress, it initiates checkpoint signaling at the forks necessary for maintaining genome stability and cell survival. To better understand the checkpoint initiation process, we have carried out a genetic screen in fission yeast by random mutation of the genome, looking for mutants defective in response to the replication stress induced by hydroxyurea. In addition to the previously reported mutant with a C-to-Y change at position 307 encoded by  tel2  ( tel2-C307Y  mutant) (Y.-J. Xu, S. Khan, A. C. Didier, M. Wozniak, et al., Mol Cell Biol 39:e00175-19, 2019, https://doi.org/10.1128/MCB.00175-19), this screen has identified six mutations in  rqh1  encoding a RecQ DNA helicase. Surprisingly, these  rqh1  mutations, except for a start codon mutation, are all in the helicase domain, indicating that the helicase activity of Rqh1 plays an important role in the replication checkpoint. In support of this notion, integration of two helicase-inactive mutations or deletion of  rqh1  generated a similar Rad3 signaling defect, and heterologous expression of human RECQ1, BLM, and RECQ4 restored the Rad3 signaling and partially rescued a  rqh1  helicase mutant. Therefore, the replication checkpoint function of Rqh1 is highly conserved, and mutations in the helicase domain of these human enzymes may cause the checkpoint defect and contribute to the cancer predisposition syndromes.
Ahamad N, Khan S, Xu YJ