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Open Access Highly Accessed Research article

Identification of novel genes involved in DNA damage response by screening a genome-wide Schizosaccharomyces pombe deletion library

Xian Pan1, Bingkun Lei1, Nan Zhou1, Biwei Feng1, Wei Yao1, Xin Zhao2, Yao Yu1* and Hong Lu1*

Author affiliations

1 State Key Laboratory of Genetic Engineering, School of Life Sciences, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433, China

2 Department of Animal Science, McGill University, Ste. Anne de Bellevue, Quebec, H9X 3V9, Canada

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Citation and License

BMC Genomics 2012, 13:662  doi:10.1186/1471-2164-13-662

Published: 23 November 2012

Abstract

Background

DNA damage response (DDR) plays pivotal roles in maintaining genome integrity and stability. An effective DDR requires the involvement of hundreds of genes that compose a complicated network. Because DDR is highly conserved in evolution, studies in lower eukaryotes can provide valuable information to elucidate the mechanism in higher organisms. Fission yeast (Schizosaccharomyces pombe) has emerged as an excellent model for DDR research in recent years. To identify novel genes involved in DDR, we screened a genome-wide S. pombe haploid deletion library against six different DNA damage reagents. The library covered 90.5% of the nonessential genes of S. pombe.

Results

We have identified 52 genes that were actively involved in DDR. Among the 52 genes, 20 genes were linked to DDR for the first time. Flow cytometry analysis of the repair defective mutants revealed that most of them exhibited a defect in cell cycle progression, and some caused genome instability. Microarray analysis and genetic complementation assays were carried out to characterize 6 of the novel DDR genes in more detail. Data suggested that SPBC2A9.02 and SPAC27D7.08c were required for efficient DNA replication initiation because they interacted genetically with DNA replication initiation proteins Abp1 and Abp2. In addition, deletion of sgf73+, meu29+, sec65+ or pab1+ caused improper cytokinesis and DNA re-replication, which contributed to the diploidization in the mutants.

Conclusions

A genome-wide screen of genes involved in DDR emphasized the key role of cell cycle control in the DDR network. Characterization of novel genes identified in the screen helps to elucidate the mechanism of the DDR network and provides valuable clues for understanding genome stability in higher eukaryotes.