RRC ID 72649
Author Ahamad N, Khan S, Xu YJ.
Title RecQ DNA Helicase Rqh1 Promotes Rad3ATR Kinase Signaling in the DNA Replication Checkpoint Pathway of Fission Yeast.
Journal Mol Cell Biol
Abstract 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.
Volume 40(17)
Published 2020-8-14
DOI 10.1128/MCB.00145-20
PII MCB.00145-20
PMID 32541066
PMC PMC7431050
MeSH Cell Cycle Checkpoints / drug effects Cell Cycle Proteins / metabolism Checkpoint Kinase 2 / genetics Checkpoint Kinase 2 / metabolism* DNA Helicases / genetics DNA Helicases / metabolism* DNA Replication* DNA, Fungal / biosynthesis* DNA, Fungal / genetics DNA, Fungal / metabolism Genomic Instability Hydroxyurea / pharmacology Protein Kinases / metabolism RecQ Helicases / genetics RecQ Helicases / metabolism Schizosaccharomyces / metabolism Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Signal Transduction / drug effects
IF 3.611
Yeast FY13012(TK7)