RESUMO

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.

Assuntos

Aspergillus nidulans/genética , Dano ao DNA/genética , Replicação do DNA/genética , Regulação Fúngica da Expressão Gênica/genética , Genes Fúngicos/fisiologia , Proteínas Quinases/genética , Aspergillus nidulans/crescimento & desenvolvimento , Aspergillus nidulans/efeitos da radiação , Dano ao DNA/efeitos da radiação , Replicação do DNA/efeitos da radiação , Regulação Enzimológica da Expressão Gênica , Fenótipo , Proteínas Quinases/metabolismo , Fase S/genética , Raios Ultravioleta