title: A point mutation in the Aspergillus nidulans sonBNup98 nuclear pore complex gene causes conditional DNA damage sensitivity.
abstract: 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 SONBnNup98 NPC protein (nucleoporin). Here we demonstrate that this mutation causes marked DNA damage sensitivity at 42 degrees . Although SONBnNup98 has roles in the G2 transition, we demonstrate that the G2 DNA damage checkpoint is functional in the sonB1 mutant at 42 degrees . The MRN complex is composed of MRE11, RAD50, and NBS1 and functions in checkpoint signaling, DNA repair, and telomere maintenance. At 42 degrees we find that the DNA damage response defect of sonB1 mutants causes synthetic lethality when combined with mutations in scaANBS1, the A. nidulans homolog of NBS1. We provide evidence that this synthetic lethality is independent of MRN cell cycle checkpoint functions or MREAMRE11-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.
authors.affiliation: Department of Molecular Genetics, Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Colin P C
authors.initials: CP
authors.lastname: De Souza
authors.forename: Shahr B
authors.initials: SB
authors.lastname: Hashmi
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Horn
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Osmani
mesh_terms: D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D001233:Aspergillus nidulans / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D016195:G2 Phase; D006657:Histones / Q000378:metabolism; D022022:Nuclear Pore / Q000502:physiology; D028861:Nuclear Pore Complex Proteins / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D016196:S Phase; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013696:Temperature
chemical_list: D029681:Arabidopsis Proteins; D004271:DNA, Fungal; D006657:Histones; D028861:Nuclear Pore Complex Proteins; D029701:Saccharomyces cerevisiae Proteins; C093350:nuclear pore complex protein 98; C427727:rad50 protein, Arabidopsis; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae