Regulation of Septum Formation in Aspergillus nidulans by a DNA Damage Checkpoint Pathway

Corresponding author: Steven D. Harris, Department of Microbiology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3205, sharris{at}nso2.uchc.edu (E-mail).

Communicating editor: R. H. DAVIS

In Aspergillus nidulans, germinating conidia undergo multiple rounds of nuclear division before the formation of the first septum. Previous characterization of temperature-sensitive sepB and sepJ mutations showed that although they block septation, they also cause moderate defects in chromosomal DNA metabolism. Results presented here demonstrate that a variety of other perturbations of chromosomal DNA metabolism also delay septum formation, suggesting that this is a general cellular response to the presence of sublethal DNA damage. Genetic evidence is provided that suggests that high levels of cyclin-dependent kinase (cdk) activity are required for septation in A. nidulans. Consistent with this notion, the inhibition of septum formation triggered by defects in chromosomal DNA metabolism depends upon Tyr-15 phosphorylation of the mitotic cdk p34^nimX. Moreover, this response also requires elements of the DNA damage checkpoint pathway. A model is proposed that suggests that the DNA damage checkpoint response represents one of multiple sensory inputs that modulates p34^nimX activity to control the timing of septum formation.

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