A multistep genomic screen identifies new genes required for repair of DNA double-strand breaks in Saccharomyces cerevisiae

BMC Genomics

Research Article

L Kevin Lewis¹  Thuy N Nguyen¹  Sunaina Sethi¹  Brian A Sanderson¹  Jennifer DeMars Tripp¹  Jennifer Summers McKinney¹  James W Westmoreland²  Michael A Resnick² 

[1] Department of Chemistry and Biochemistry, Texas State University, 78666, San Marcos, TX, USA;Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, 27709, Research Triangle Park, NC, USA;

关键词: EcoRI;    Homologous recombination;    End-joining;    Double-strand break;    Bleomycin;    MMS;    Radiation;    RAD52;    Gene ontology (GO);    Overlapping genes;   

DOI  :  10.1186/1471-2164-14-251

 received in 2013-01-04, accepted in 2013-03-26,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundEfficient mechanisms for rejoining of DNA double-strand breaks (DSBs) are vital because misrepair of such lesions leads to mutation, aneuploidy and loss of cell viability. DSB repair is mediated by proteins acting in two major pathways, called homologous recombination and nonhomologous end-joining. Repair efficiency is also modulated by other processes such as sister chromatid cohesion, nucleosome remodeling and DNA damage checkpoints. The total number of genes influencing DSB repair efficiency is unknown.ResultsTo identify new yeast genes affecting DSB repair, genes linked to gamma radiation resistance in previous genome-wide surveys were tested for their impact on repair of site-specific DSBs generated by in vivo expression of EcoRI endonuclease. Eight members of the RAD52 group of DNA repair genes (RAD50, RAD51, RAD52, RAD54, RAD55, RAD57, MRE11 and XRS2) and 73 additional genes were found to be required for efficient repair of EcoRI-induced DSBs in screens utilizing both MATa and MATα deletion strain libraries. Most mutants were also sensitive to the clastogenic chemicals MMS and bleomycin. Several of the non-RAD52 group genes have previously been linked to DNA repair and over half of the genes affect nuclear processes. Many proteins encoded by the protective genes have previously been shown to associate physically with each other and with known DNA repair proteins in high-throughput proteomics studies. A majority of the proteins (64%) share sequence similarity with human proteins, suggesting that they serve similar functions.ConclusionsWe have used a genetic screening approach to detect new genes required for efficient repair of DSBs in Saccharomyces cerevisiae. The findings have spotlighted new genes that are critical for maintenance of genome integrity and are therefore of greatest concern for their potential impact when the corresponding gene orthologs and homologs are inactivated or polymorphic in human cells.

【 授权许可】

Unknown   
© McKinney et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.