Originally published as Genetics Published Articles Ahead of Print on October 8, 2006.

Genetics, Vol. 174, 1881-1893, December 2006, Copyright © 2006
doi:10.1534/genetics.106.063438

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

Colin P. C. De Souza, Shahr B. Hashmi, Kevin P. Horn¹ and Stephen A. Osmani²

Department of Molecular Genetics, Ohio State University, Columbus, Ohio 43210

² Corresponding author: Department of Molecular Genetics, Ohio State University, Columbus, OH 43210.
E-mail: osmani.2{at}osu.edu

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 G₂ transition, we demonstrate that the G₂ 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° we 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.

This article has been cited by other articles:

				B. Palancade, X. Liu, M. Garcia-Rubio, A. Aguilera, X. Zhao, and V. Doye Nucleoporins Prevent DNA Damage Accumulation by Modulating Ulp1-dependent Sumoylation Processes Mol. Biol. Cell, August 1, 2007; 18(8): 2912 - 2923. [Abstract] [Full Text] [PDF]

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