Identification of New DNA Damage Response Proteins Using a Genetic Screen.

Larson, J. R. and Osmani, S. A.

Author address: 

The Ohio State University, Columbus, Ohio.

Abstract: 

The cellular response to DNA damage involves many well characterized proteins. However, there are likely still unidentified proteins that play important roles in these pathways. For example, several nuclear pore complex proteins (Nups) are required for resistance to DNA damage via unknown mechanisms. SonB is an essential Nup in Aspergillus nidulans and a mutant allele of this protein that confers temperature-dependent DNA damage sensitivity was previously isolated in a genetic screen for suppressors of the temperature-sensitive nimA1 mitotic kinase mutation (De Souza et al., 2006 Genetics 174, 1881-93). Importantly, subsequent analyses showed that SonB is involved in a novel DNA damage response pathway. No other proteins have yet been linked to this pathway. To identify other proteins involved with SonB we have undertaken a genetic screen for DNA damage-sensitive nimA1 suppressors and have isolated two previously uncharacterized proteins, AN1902 and a new Nup, AN11115. AN11115-GFP localizes to the nuclear periphery throughout the cell cycle and at mitosis forms several distinct foci similar to another Nup, Pom152. Deletion of AN11115 causes marked temperature-dependent DNA damage sensitivity, similar to SonB mutants. Affinity purification and mass spec analysis of AN11115 identified AN1902 thus linking together the genetic and biochemical data. Further studies will add to our understanding of how the nuclear pore complex and the NIMA kinase are involved in the DNA damage response and allow us to map out this novel DNA damage response pathway. (Supported by a NIH National Research Service Award (T32CA106196) to JRL)
2011

abstract No: 

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Full conference title: 

26th Fungal Genetics Conference
    • Fungal Genetics Conference 26th (2005)