title: Hyphal differentiation induced via a DNA damage checkpoint-dependent pathway engaged in crosstalk with nutrient stress signaling in Schizosaccharomyces japonicus.
abstract: DNA damage response includes DNA repair, nucleotide metabolism and even a control of cell fates including differentiation, cell death pathway or some combination of these. The responses to DNA damage differ from species to species. Here we aim to delineate the checkpoint pathway in the dimorphic fission yeast Schizosaccharomyces japonicus, where DNA damage can trigger a differentiation pathway that is a switch from a bidirectional yeast growth mode to an apical hyphal growth mode, and the switching is regulated via a checkpoint kinase, Chk1. This Chk1-dependent switch to hyphal growth is activated with even low doses of agents that damage DNA; therefore, we reasoned that this switch may depend on other genes orthologous to the components of the classical Sz. pombe Chk1-dependent DNA checkpoint pathway. As an initial test of this hypothesis, we assessed the effects of mutations in Sz. japonicus orthologs of Sz. pombe checkpoint genes on this switch from bidirectional to hyphal growth. The same set of DNA checkpoint genes was confirmed in Sz. japonicus. We tested the effect of each DNA checkpoint mutants on hyphal differentiation by DNA damage. We found that the Sz. japonicus hyphal differentiation pathway was dependent on Sz. japonicus orthologs of Sz. pombe checkpoint genes-(SP)rad3, (SP)rad26, (SP)rad9, (SP)rad1, (SP)rad24, (SP)rad25, (SP)crb2, and (SP)chk1-that function in the DNA damage checkpoint pathway, but was not dependent on orthologs of two Sz. pombe genes-(SP)cds1 or (SP)mrc1-that function in the DNA replication checkpoint pathway. These findings indicated that although the role of each component of the DNA damage checkpoint and DNA replication checkpoint is mostly same between the two fission yeasts, the DNA damage checkpoint was the only pathway that governed DNA damage-dependent hyphal growth. We also examined whether DNA damage checkpoint signaling engaged in functional crosstalk with other hyphal differentiation pathways because hyphal differentiation can also be triggered by nutritional stress. Here, we discovered genetic interactions that indicated that the cAMP pathway engaged in crosstalk with Chk1-dependent signaling.
authors.affiliation: Department of Genetics, Graduate University for Advanced Studies, Sokendai, Hayama, Miura District, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Furuya
authors.forename: Hironori
authors.initials: H
authors.lastname: Niki
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D000071877:Checkpoint Kinase 1; D003470:Culture Media / Q000378:metabolism; D004249:DNA Damage; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D018816:Genes, cdc; D025301:Hyphae / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D018741:Replication Origin; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D048948:14-3-3 Proteins; D003470:Culture Media; D004271:DNA, Fungal; D005656:Fungal Proteins; D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C000605873:Chk1 protein, S pombe