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Abstract
The DNA damage response (DDR) is a conserved mechanism that maintains genomic integrity in living organisms. The DDR promotes repair of DNA lesions, activation of cell cycle checkpoints and, if the damage is not repaired, induction of programmed cell death (PCD). The results presented here show that the DDR of the filamentous fungus Aspergillus nidulans is correlated both with PCD and with hyphal morphogenesis.
We demonstrate that PCD can be induced in A. nidulans by farnesol as a result of antagonist fungal interactions. Farnesol induced morphological features characteristic of apoptosis, which was dependent on mitochondria, reactive oxygen species (ROS), the FadA heterotrimeric G protein complex, and the Poly(ADP)-ribose polymerase homolog (PrpA). Further studies demonstrated that PrpA is an essential protein that functions early in the DDR. In addition, PrpA was shown to be required for asexual development and hyphal morphogenesis.
Another A. nidulans DDR component correlated to hyphal morphology was AtmA, the homolog of the Ataxia telangiectasia mutated (ATM) kinase. ATM is a phosphatidyl-3-kinase-related protein kinase (PIKK) that functions as a central regulator of the DDR in eukaryotic cells. We demonstrated that besides its role in the DDR, AtmA is involved in the generation of a stable axis of hyphal polarity. Finally, we show that the morphological defects caused by the absence of PrpA and AtmA are accompanied by disruption of reactive oxygen species (ROS) localization. An ROS gradient localizes to the hyphal tip and appears to regulate specification of the primary axis of hyphal polarity.
In conclusion, we propose that unique features of the fungal DDR, such as the links to hyphal cell death and morphogenesis, are potential targets for the therapeutic manipulation of fungal growth.
