title: Deficiency of the Arabidopsis helicase RTEL1 triggers a SOG1-dependent replication checkpoint in response to DNA cross-links.
abstract: To maintain genome integrity, DNA replication is executed and regulated by a complex molecular network of numerous proteins, including helicases and cell cycle checkpoint regulators. Through a systematic screening for putative replication mutants, we identified an Arabidopsis thaliana homolog of human Regulator of Telomere Length 1 (RTEL1), which functions in DNA replication, DNA repair, and recombination. RTEL1 deficiency retards plant growth, a phenotype including a prolonged S-phase duration and decreased cell proliferation. Genetic analysis revealed that rtel1 mutant plants show activated cell cycle checkpoints, specific sensitivity to DNA cross-linking agents, and increased homologous recombination, but a lack of progressive shortening of telomeres, indicating that RTEL1 functions have only been partially conserved between mammals and plants. Surprisingly, RTEL1 deficiency induces tolerance to the deoxynucleotide-depleting drug hydroxyurea, which could be mimicked by DNA cross-linking agents. This resistance does not rely on the essential replication checkpoint regulator WEE1 but could be blocked by a mutation in the SOG1 transcription factor. Taken together, our data indicate that RTEL1 is required for DNA replication and that its deficiency activates a SOG1-dependent replication checkpoint.
authors.affiliation: Department of Plant Systems Biology, VIB, B-9052 Gent, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, B-9052 Gent, Belgium.
authors.forename: Zhubing
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Plant Systems Biology, VIB, B-9052 Gent, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, B-9052 Gent, Belgium.
authors.forename: Toon
authors.initials: T
authors.lastname: Cools
authors.affiliation: Department of Plant Systems Biology, VIB, B-9052 Gent, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, B-9052 Gent, Belgium.
authors.forename: Pooneh
authors.initials: P
authors.lastname: Kalhorzadeh
authors.affiliation: Department of Plant Systems Biology, VIB, B-9052 Gent, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, B-9052 Gent, Belgium.
authors.forename: Jefri
authors.initials: J
authors.lastname: Heyman
authors.affiliation: Department of Plant Systems Biology, VIB, B-9052 Gent, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, B-9052 Gent, Belgium lieven.deveylder@psb.vib-ugent.be.
authors.forename: Lieven
authors.initials: L
authors.lastname: De Veylder
mesh_terms: D017360:Arabidopsis / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D004265:DNA Helicases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000235:genetics / Q000502:physiology; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029681:Arabidopsis Proteins; D010940:Plant Proteins; C561308:SOG1 protein, Arabidopsis; D014157:Transcription Factors; D004265:DNA Helicases; C000602077:RTEL1 protein, Arabidopsis