A Point Mutation in the Aspergillus nidulans sonB super(Nup98) Nuclear Pore Complex Gene Causes Conditional DNA Damage Sensitivity

• Published in: Genetics (Austin) 2006-12, Vol.174 (4)
• Main Authors: De Souza, Colin PC, Hashmi, Shahr B, Horn, Kevin P, Osmani, Stephen A
• Format: Article
• Language: English
• Subjects: Aspergillus nidulans
• ISSN: 0016-6731
• DOI: 10.1534/genetics.106.063438

The nuclear pore complex (NPC) is embedded in the nuclear envelope where it mediates transport between the cytoplasm and nucleus and helps to organize nuclear architecture. We previously isolated sonB1, a mutation encoding a single amino acid substitution within the Aspergillus nidulans SONBn super(Nup98) NPC protein (nucleoporin). Here we demonstrate that this mutation causes marked DNA damage sensitivity at 42 degree . Although SONBn super(Nup98) has roles in the G sub(2) transition, we demonstrate that the G sub(2) DNA damage checkpoint is functional in the sonB1 mutant at 42 degree . The MRN complex is composed of MRE11, RAD50, and NBS1 and functions in checkpoint signaling, DNA repair, and telomere maintenance. At 42 degree we find that the DNA damage response defect of sonB1 mutants causes synthetic lethality when combined with mutations in scaA super(NBS1), the A. nidulans homolog of NBS1. We provide evidence that this synthetic lethality is independent of MRN cell cycle checkpoint functions or MREA super(MRE11)-mediated DNA repair functions. We also demonstrate that the single A. nidulans histone H2A gene contains the C-terminal SQE motif of histone H2AX isoforms and that this motif is required for the DNA damage response. We propose that the sonB1 nucleoporin mutation causes a defect in a novel part of the DNA damage response.