The csnD-E signalosome genes are involved in the Aspergillus nidulans DNA damage response.

Iran Malavazi , Joel F. Lima ,Marcia R.V.Z.K. Fagundes , Marcela Savoldi , Maria H. S. Goldman , Gerhard Braus and Gustavo H. Goldman .

Author address: 

Faculdade de Ciëncias Farmacëuticas de Ribeirão Preto and Faculdade de Filosofia, Ciëncias e Letras de Ribeirão Preto, Universidade de São Paulo, Brazil. Department of Microbiology and Genetics, Institute for Microbiology and Genetics, Georg-Aug

Abstract: 

The signalosome (CSN) is a conserved complex involved in protein turnover and eukaryotic development, and is also required to activate ribonucleotide reductase for DNA synthesis. In A. nidulans, csnD and csnE, are key regulators of sexual development. We investigated if these genes are involved in the DNA damage response. The growth of the csnD-E deletion mutants is reduced by sub-inhibitory concentrations of camptothecin (CPT) and 4-nitroquinoline oxide (4-NQO). In A. nidulans, septum formation is inhibited by DNA damage in a checkpoint-dependent manner. Nevertheless, septation is not inhibited in the csnD-E deletion mutants upon DNA damage caused by methyl methane sulfonate (MMS). The csnD mRNA expression was induced by CPT, MMS, bleomycin (BLEO) (about 3-fold), and 4-NQO (9-fold). The csnE gene encoding the deneddylase activity which is required to modify E3 SCF ubiquitin ligases, has high levels of mRNA expression induced by all drugs (from 10-fold, CPT to 37-fold, 4-NQO). Germinating conidia of csnD-E deletion strains are more sensitive to ultraviolet light than the corresponding wild type strain. We constructed double mutants with csnD-E deletion, npkA and uvsB . The NpkA is a cdc2-related kinase that is involved in the S-phase. The double ATR csnD npkA and csnE npkA mutants are much more sensitive to DNA damaging agents than the respective single mutants. However, the intra-S-phase and DNA replication checkpoints are intact in these mutants. Our results suggest that csnD-E genes are involved in the DNA damage response and that NpkA genetically interacts with the CSN. Financial support: FAPESP and CNPq, Brazi
2005

abstract No: 

39.

Full conference title: 

23rd Fungal Genetics Conference
    • Fungal Genetics Conference 23rd (2002)