The nuv mutants of Aspergillus comprise a collection of strains sensitive to a broad range of DNA damaging agents. Amongst them, the nuvF102 mutant is abnormally sensitive to alkylating agents and 4NQO, but appears normal for mitotic and meiotic recombination. Unlike most of the other nuv mutants, it is also sensitive to hydroxyurea and this sensitivity can be supressed by mitotic inhibitors such as benomyl. We show that the mutant exhibits abnormal nuclear morphology following exposure to a variety of DNA damaging agents, and that this correlates with a premature resumption of post-damage DNA synthesis. In the mutant cell, both DNA synthesis and mitosis appear to be halted correctly by DNA damage. However, post-damage DNA synthesis is delayed much less than in wild-type, and the cell also enters mitosis early. The observation that the mutants are sensitive to HU suggests that recovery from a block to DNA replication is also aberrant, while the effects of benomyl indicate that the consequences of these aberrations may be overcome if mitosis is delayed. The nuvF102 gene has been cloned and sequenced, and the gene product displays little homology to proteins of known function in the databases. There is homology across a small region to the Sta3 group of signal transduction / transcription activating proteins, and the protein also contains a large motif that is repeated in the highly inducible yeast protein Ddr48. We show that nimA and nimX kinase activities appear unaffected in the mutant cells, and we propose a model in which nuvF plays a role in the rad53 - mec1 pathway to control both mitotic arrest and the resumption of DNA synthesis.
Fungal Genet. Newsl. 46 (Supl):
Full conference title:
Fungal Genetics Conference 20th
- Fungal Genetics Conference 20th (1999)