title: Genome-wide mapping of unexplored essential regions in the Saccharomyces cerevisiae genome: evidence for hidden synthetic lethal combinations in a genetic interaction network.
abstract: Despite systematic approaches to mapping networks of genetic interactions in Saccharomyces cerevisiae, exploration of genetic interactions on a genome-wide scale has been limited. The S. cerevisiae haploid genome has 110 regions that are longer than 10 kb but harbor only non-essential genes. Here, we attempted to delete these regions by PCR-mediated chromosomal deletion technology (PCD), which enables chromosomal segments to be deleted by a one-step transformation. Thirty-three of the 110 regions could be deleted, but the remaining 77 regions could not. To determine whether the 77 undeletable regions are essential, we successfully converted 67 of them to mini-chromosomes marked with URA3 using PCR-mediated chromosome splitting technology and conducted a mitotic loss assay of the mini-chromosomes. Fifty-six of the 67 regions were found to be essential for cell growth, and 49 of these carried co-lethal gene pair(s) that were not previously been detected by synthetic genetic array analysis. This result implies that regions harboring only non-essential genes contain unidentified synthetic lethal combinations at an unexpectedly high frequency, revealing a novel landscape of genetic interactions in the S. cerevisiae genome. Furthermore, this study indicates that segmental deletion might be exploited for not only revealing genome function but also breeding stress-tolerant strains.
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
authors.forename: Saeed
authors.initials: S
authors.lastname: Kaboli
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamakawa
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sunada
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
authors.forename: Tao
authors.initials: T
authors.lastname: Takagaki
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sasano
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
authors.forename: Minetaka
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita-shi, Osaka 565-0871, Japan harashima@bio.eng.osaka-u.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Harashima
mesh_terms: D002872:Chromosome Deletion; D002874:Chromosome Mapping; D005800:Genes, Fungal; D005804:Genes, Lethal; D016681:Genome, Fungal; D012441:Saccharomyces cerevisiae / Q000235:genetics*
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