Genetic interactions of the Aspergillus nidulans atmAATM homolog with different components of the DNA damage response pathway.
Ataxia telangiectasia mutated (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 homolog 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) loss 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 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 DeltaatmA, DeltauvsB, DeltachkA, and DeltachkB. 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.
Malavazi
Iran
I
Faculdade de Ciências de Ribeirão Preto, Universidade de São Paulo, São Paulo 14040-903, Brazil.
Lima
Joel Fernandes
JF
de Castro
Patrícia Alves
PA
Savoldi
Marcela
M
de Souza Goldman
Maria Helena
MH
Goldman
Gustavo Henrique
GH
D001233:Aspergillus nidulans / Q000166:cytology / Q000235:genetics*; D001260:Ataxia Telangiectasia / Q000201:enzymology / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics; D003470:Culture Media; D004249:DNA Damage; D017931:DNA Primers; D004271:DNA, Fungal / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005838:Genotype; D006801:Humans; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012331:RNA, Fungal / Q000235:genetics / Q000302:isolation & purification; D025521:Tumor Suppressor Proteins / Q000235:genetics; D014498:Uracil / Q000378:metabolism; D014529:Uridine / Q000378:metabolism
D018797:Cell Cycle Proteins; D003470:Culture Media; D017931:DNA Primers; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D012331:RNA, Fungal; D025521:Tumor Suppressor Proteins; D014498:Uracil; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D014529:Uridine