Genetics, Vol. 167, 1629-1641, August 2004, Copyright © 2004
doi:10.1534/genetics.103.024166

The Aspergillus nidulans npkA Gene Encodes a Cdc2-Related Kinase That Genetically Interacts With the UvsB^ATR Kinase

Marcia R. V. Z. Kress Fagundes^*, Joel Fernandes Lima^*, Marcela Savoldi^*, Iran Malavazi^*, Roy E. Larson, Maria H. S. Goldman and Gustavo H. Goldman^*,1

^* 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
Faculdade de Medicina de Ribeirão Preto, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil
Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil

¹ Corresponding author: Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café S/N, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil.
E-mail: ggoldman{at}usp.br

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 p34^Cdc2-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 uvsB^ATR 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 npkA mutation can partially suppress HU sensitivity caused by the uvsB^ATR and uvsD153^ATRIP checkpoint mutations. We demonstrated that the A. nidulans uvsB^ATR gene is involved in DNA replication and the intra-S-phase checkpoints and that the npkA 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.

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