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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 UvsBATR 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 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 
npkA mutation can partially suppress HU sensitivity caused by the uvsBATR 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 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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