Genetic interactions of the Aspergillus nidulans atmA^ATM homologue with different components of the DNA damage response pathway

ATM is a phosphatidyl-3-kinase-related protein kinase that functions as a central regulator of the DNA damage response in eukaryotic cells. In humans, mutations in ATM cause the devastating neurodegenerative disease Ataxia Telangiectasia. Previously, we characterized the homologue of ATM (AtmA) in the filamentous fungus Aspergillus nidulans. In addition to its expected role in the DNA damage response, we found that AtmA is also required for polarized hyphal growth. Here, we extended these studies by investigating which components of the DNA damage response pathway are interacting with AtmA. The AtmA^ATM lost of function caused synthetic lethality when combined with mutation in UvsB^ATR. Our results suggest that AtmA and UvsB are interacting and they are probably partially redundant in terms of DNA damage sensing and/or repairing, morphological checkpoints, and polar growth. We identified and inactivated A. nidulans chkA^CHK1 and chkB^CHK2 genes. These genes are also redundantly involved in A. nidulans DNA damage response. We constructed several combinations of double mutants for atmA, uvsB, chkA, and chkB. We observed a complex genetic relationship with these mutations during the DNA replication checkpoint and DNA damage response. Finally, we observed epistatic and synergistic interactions between AtmA, and bimE^APC1, ankA^WEE1 and the cdc2-related kinase npkA, at S-phase checkpoint and in response to DNA damaging agents.

Key Words: ATM kinase, Aspergillus nidulans, CHK1, CHK2, DNA damage response

Online ISS 1091-6490
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