Aspergillus nidulans uvsBATR and scaANBS1 genes show genetic interactions during recovery from replication stress and DNA damage |
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Authors: | Fagundes Marcia Regina von Zeska Kress Semighini Camile P Malavazi Iran Savoldi Marcela de Lima Joel Fernandes de Souza Goldman Maria Helena Harris Steven D Goldman Gustavo Henrique |
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Affiliation: | Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeir?o Preto, Universidade de S?o Paulo, Av. do Café S/N, CEP 14040-903, Ribeir?o Preto, S?o Paulo, Brazil. |
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Abstract: | The ATM/ATR kinases and the Mre11 (Mre11-Rad50-Nbs1) protein complex are central players in the cellular DNA damage response. Here we characterize possible interactions between Aspergillus nidulans uvsB(ATR) and the Mre11 complex (scaA(NBS1)). We demonstrate that there is an epistatic relationship between uvsB(ATR), the homolog of the ATR/MEC1 gene, and scaA(NBS1), the homolog of the NBS1/XRS2 gene, for both repair and checkpoint functions and that correct ScaA(NBS1) expression during recovery from replication stress depends on uvsB(ATR). In addition, we also show that the formation of UvsC foci during recovery from replication stress is dependent on both uvsB(ATR) and scaA(NBS1) function. Furthermore, ScaA(NBS1) is also dependent on uvsB(ATR) for nuclear focus formation upon the induction of DNA double-strand breaks by phleomycin. Our results highlight the extensive genetic interactions between UvsB and the Mre11 complex that are required for S-phase progression and recovery from DNA damage. |
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