Genes required for ionizing radiation resistance in yeast

Abstract

The ability of Saccharomyces cerevisiae to tolerate ionizing radiation damage requires many DNA-repair and checkpoint genes, most having human orthologs. A genome-wide screen of diploid mutants homozygous with respect to deletions of 3,670 nonessential genes revealed 107 new loci that influence gamma-ray sensitivity. Many affect replication, recombination and checkpoint functions. Nearly 90% were sensitive to other agents, and most new genes could be assigned to the following functional groups: chromatin remodeling, chromosome segregation, nuclear pore formation, transcription, Golgi/vacuolar activities, ubiquitin-mediated protein degradation, cytokinesis, mitochondrial activity and cell wall maintenance. Over 50% share homology with human genes, including 17 implicated in cancer, indicating that a large set of newly identified human genes may have related roles in the toleration of radiation damage.

Ccr4 contributes to tolerance of replication stress through control ofCRT1mRNA poly(A) tail length

“…Other recent reports have also implicated Ccr4 in resistance to HU-induced replication stress (Bennett et al, 2001;Westmoreland et al, 2004;Traven et al, 2005). Because our genetic analysis shows that mec1, rad53 and dun1⌬ mutants, but not chk1⌬ mutants, are hypersensitized to HU upon deletion of CCR4, it appears Ccr4 operates in parallel to the Mec1-Rad53-Dun1 pathway to resolve DNA replication stress, perhaps in concert with Chk1.…”

“…In particular, Hartman and Tippery quantitatively profiled arrayed deletion strains for sensitivity to either 50 mM or 150 mM HU (Hartman and Tippery, 2004); Parsons et al (Parsons et al, 2004) examined arrayed strains robotically pinned to solid media containing 100 mM HU; Bennett et al (Bennett et al, 2001) identified diploid deletion strains cross-sensitive to both ionizing radiation (primary screen) and 100 mM HU (secondary screen). We compared our confirmed HU-sensitive deletion strains (i.e.…”

“…(A) Gene deletion strains hypersensitive to hydroxyurea (HU) identified by the approaches of Bennett et al, Hartman and Tippery, Parsons et al and this study were compiled to identify the shared HU sensitive strains (Bennett et al, 2001;Hartman and Tippery, 2004;Parsons et al, 2004). Number of gene deletions shared between datasets (intersections) or unique to each individual dataset (peripheries) are indicated.…”

Chromatin disassembly and reassembly during DNA repair

“…Inactivation in Saccharomyces cerevisiae causes sensitivity to UV [39], gamma irradiation [40], HO endonuclease, alkylating agents, and radiomimetics [41]. Arabidopsis mutants of CAF-1 are sensitive to the alkylating agent MMS [42].…”

“…RSC rsc1 and rsc2 Saccharomyces cerevisiae mutants are sensitive to gamma irradiation [40], and to radiomimetics, alkylating agents and UV when grown at their semipermissive temperatures [43][44][45]. SWI/SNF snf5 and snf2 Saccharomyces cerevisiae mutants are sensitive to radiomimetics and are moderately sensitive to alkylating agents and UV irradiation [45].…”