Strict regulation of cdk activity has been shown to be important for cytokinesis in a variety of eukaryotic systems. In the filamentous fungus Aspergillus nidulans, the cdk encoded by the nimX gene has been shown to be involved in regulating cytokinesis. Genetic evidence suggests that the ability to separate mitosis and septum formation depends upon a threshold level of NIMX activity. A transient inhibition of NIMX activity by the activation of the DNA damage checkpoint pathway results in a significant delay in septum formation. This supports the idea that germlings must reach a threshhold level of NIMX activity at a certain point during inteiphase in order to initiate septum formation. In order to identify additional components of the pathway regulating septum formation, we have initiated a genetic screen for extragenic suppressors of the Ts nimT23 mutation, which results in inactivation of the NIMX-activating tyrosine phosphatase NIMT. We have counter-screened 500 suppressors of the nimT23 mutation for HU sensitivity in order to distinguish those mutants which may be defective in the checkpoint pathways which respond to DNA damage or unreplicated DNA. We have isolated 7 HU sensitive mutants which fall into three linkage groups (designated sntA, sntB and sntQ and are distinct from alleles of nimX and ankA (which encodes the A. nidulans homolog of S. pombe Wee lp). snt mutations allow germlings to undergo septum formation before the critical cell size is reached and in the presence of DNA damage generated by mutation (sepB3) and by the bi-functional alkylating agent diepoxyoctane (DEO). The snt mutations have different effects on cell cycle checkpoints and result in decreased phosphorylation on Tyrosine-15 of NIMX.
Fungal Genet. Newsl. 46 (Supl):
Full conference title:
Fungal Genetics Conference 20th
- Fungal Genetics Conference 20th (1999)