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 Nup98 NPC protein (nucleoporin). Here we demonstrate that this mutation causes marked DNA damage sensitivity at 42°. Although SONBn Nup98 has roles in the G 2 transition, we demonstrate that the G 2 DNA damage checkpoint is functional in the sonB1 mutant at 42°. The MRN complex is composed of MRE11, RAD50, and NBS1 and functions in checkpoint signaling, DNA repair, and telomere maintenance. At 42°w e find that the DNA damage response defect of sonB1 mutants causes synthetic lethality when combined with mutations in scaA NBS1 , the A. nidulans homolog of NBS1. We provide evidence that this synthetic lethality is independent of MRN cell cycle checkpoint functions or MREA 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.

The Aspergillus nidulans NIMA kinase is essential for mitotic entry. At restrictive temperature, temperature-sensitive nimA alleles arrest in G2, before accumulation of NIMA in the nucleus. We performed a screen for extragenic suppressors of the nimA1 allele and isolated two cold-sensitive son (suppressor of nimA1) mutants. The sonA1 mutant encoded a nucleoporin that is a homolog of yeast Gle2/Rae1. We have now cloned SONB, a second nucleoporin genetically interacting with NIMA. sonB is essential and encodes a homolog of the human NUP98/NUP96 precursor. Similar to NUP98/NUP96, SONBNUP98/NUP96 is autoproteolytically cleaved to generate SONBNUP98 and SONBNUP96. SONBNUP98 localizes to the nuclear pore complex and contains a GLEBS domain (Gle2 binding sequence) that binds SONAGLE2. A point mutation within the GLEBS domain of SONB1NUP98 suppresses the temperature sensitivity of the nimA1 allele and compromises the physical interaction between SONAGLE2 and SONB1NUP98. The sonB1 mutation also causes sensitivity to hydroxyurea. We isolated the histone H2A-H2B gene pair as a copy-number suppressor of sonB1 cold sensitivity and hydroxyurea sensitivity. The data suggest that the nucleoporins SONAGLE2 and SONBNUP98 and the NIMA kinase interact and regulate nuclear accumulation of mitotic regulators to help promote mitosis.