title: The Aspergillus nidulans npkA gene encodes a Cdc2-related kinase that genetically interacts with the UvsBATR kinase.
abstract: The DNA damage response is a protective mechanism that ensures the maintenance of genomic integrity. We have used Aspergillus nidulans as a model system to characterize the DNA damage response caused by the antitopoisomerase I drug, camptothecin. We report the molecular characterization of a p34Cdc2-related gene, npkA, from A. nidulans. The npkA gene is transcriptionally induced by camptothecin and other DNA-damaging agents, and its induction in the presence of camptothecin is dependent on the uvsBATR gene. There were no growth defects, changes in developmental patterns, increased sensitivity to DNA-damaging agents, or effects on septation or growth rate in the A. nidulans npkA deletion strain. However, the DeltanpkA mutation can partially suppress HU sensitivity caused by the DeltauvsBATR and uvsD153ATRIP checkpoint mutations. We demonstrated that the A. nidulans uvsBATR gene is involved in DNA replication and the intra-S-phase checkpoints and that the DeltanpkA mutation can suppress its intra-S-phase checkpoint deficiency. There is a defect in both the intra-S-phase and DNA replication checkpoints due to the npkA inactivation when DNA replication is slowed at 6 mm HU. Our results suggest that the npkA gene plays a role in cell cycle progression during S-phase as well as in a DNA damage signal transduction pathway in A. nidulans.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Marcia R V Z Kress
authors.initials: MR
authors.lastname: Fagundes
authors.forename: Joel Fernandes
authors.initials: JF
authors.lastname: Lima
authors.forename: Marcela
authors.initials: M
authors.lastname: Savoldi
authors.forename: Iran
authors.initials: I
authors.lastname: Malavazi
authors.forename: Roy E
authors.initials: RE
authors.lastname: Larson
authors.forename: Maria H S
authors.initials: MH
authors.lastname: Goldman
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Goldman
mesh_terms: D000595:Amino Acid Sequence; D001233:Aspergillus nidulans / Q000201:enzymology / Q000235:genetics*; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D004249:DNA Damage; D017931:DNA Primers; D004264:DNA Topoisomerases, Type I / Q000235:genetics; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D059004:Topoisomerase I Inhibitors
chemical_list: D017931:DNA Primers; D059004:Topoisomerase I Inhibitors; D016203:CDC2 Protein Kinase; D004264:DNA Topoisomerases, Type I