Identification of a Topoisomerase I Mutant, scsA1, as an Extragenic Suppressor of a Mutation in scaA^NBS1, the Apparent Homolog of Human Nibrin in Aspergillus nidulans

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

Communicating editor: J. J. LOROS

The Mre11-Rad50-Nbs1 protein complex has emerged as a central player in the human cellular DNA damage response, and recent observations suggest that these proteins are at least partially responsible for the linking of DNA damage detection to DNA repair and cell cycle checkpoint functions. Mutations in scaA^NBS1, which encodes the apparent homolog of human nibrin in Aspergillus nidulans, inhibit growth in the presence of the antitopoisomerase I drug camptothecin. This article describes the selection and characterization of extragenic suppressors of the scaA1 mutation, with the aim of identifying other proteins that interfere with the pathway or complex in which the ScaA would normally be involved. Fifteen extragenic suppressors of the scaA1 mutation were isolated. The topoisomerase I gene can complement one of these suppressors. Synergistic interaction between the scaA^NBS1 and scsA^TOP1 genes in the presence of DNA-damaging agents was observed. Overexpression of topoisomerase I in the scaA1 mutant causes increased sensitivity to DNA-damaging agents. The scsA^TOP1 and the scaA^NBS1 gene products could functionally interact in pathways that either monitor or repair DNA double-strand breaks.

This article has been cited by other articles:

				I. Malavazi, M. Savoldi, S. M. Z. Di Mauro, C. F. M. Menck, S. D. Harris, M. H. d. S. Goldman, and G. H. Goldman Transcriptome Analysis of Aspergillus nidulans Exposed to Camptothecin-Induced DNA Damage. Eukaryot. Cell, October 1, 2006; 5(10): 1688 - 1704. [Abstract] [Full Text] [PDF]

				J. F. Lima, I. Malavazi, M. R. von Zeska Kress Fagundes, M. Savoldi, M. H. S. Goldman, E. Schwier, G. H. Braus, and G. H. Goldman The csnD/csnE Signalosome Genes Are Involved in the Aspergillus nidulans DNA Damage Response Genetics, November 1, 2005; 171(3): 1003 - 1015. [Abstract] [Full Text] [PDF]

				M. R. v. Z. K. Fagundes, C. P. Semighini, I. Malavazi, M. Savoldi, J. F. de Lima, M. H. de Souza Goldman, S. D. Harris, and G. H. Goldman Aspergillus nidulans uvsBATR and scaANBS1 Genes Show Genetic Interactions during Recovery from Replication Stress and DNA Damage Eukaryot. Cell, July 1, 2005; 4(7): 1239 - 1252. [Abstract] [Full Text] [PDF]

				M. R. V. Z. K. Fagundes, J. F. Lima, M. Savoldi, I. Malavazi, R. E. Larson, M. H. S. Goldman, and G. H. Goldman The Aspergillus nidulans npkA Gene Encodes a Cdc2-Related Kinase That Genetically Interacts With the UvsBATR Kinase Genetics, August 1, 2004; 167(4): 1629 - 1641. [Abstract] [Full Text] [PDF]