title: Homologous recombination is responsible for cell death in the absence of the Sgs1 and Srs2 helicases.
abstract: DNA helicases are involved in many aspects of DNA metabolism, including transcription, replication, recombination and repair. In the yeast Saccharomyces cerevisiae, the absence of the Sgs1 helicase results in genomic instability and accelerated ageing. In human cells, mutations in orthologues of SGS1 lead to Bloom (BS), Werner (WS) or Rothmund-Thomson (RTS) syndromes, which are rare, autosomal recessive diseases characterized by genetic instability associated with cancer predisposition. Although data concerning these human diseases are accumulating, there is still no clear idea of the function of the proteins involved. Here we show that sgs1Delta mutants are deficient in DNA repair and are defective for induced recombination events that involve homologous chromosomes. The role of homologous recombination is further evidenced in haploid cells in which both Sgs1p and Srs2p are absent. Yeast SRS2 encodes another DNA helicase involved in the maintenance of genome integrity. Our data suggest that some defects observed in BS, WS or RTS are the consequence of unrestrained recombination.
authors.affiliation: CEA de Fontenay-aux-Roses, UMR 217 CNRS-CEA/DSV/DRR/LERA, 92265 Fontenay-aux-Roses, France. Serge.Gangloff@cea.fr
authors.forename: S
authors.initials: S
authors.lastname: Gangloff
authors.forename: C
authors.initials: C
authors.lastname: Soustelle
authors.forename: F
authors.initials: F
authors.lastname: Fabre
mesh_terms: D001816:Bloom Syndrome / Q000235:genetics; D002455:Cell Division / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004265:DNA Helicases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005720:Gamma Rays; D005800:Genes, Fungal / Q000235:genetics / Q000502:physiology; D005804:Genes, Lethal / Q000235:genetics; D006238:Haploidy; D006801:Humans; D009154:Mutation / Q000235:genetics; D051135:Rad51 Recombinase; D011836:Radiation Tolerance / Q000235:genetics; D053484:RecQ Helicases; D011995:Recombination, Genetic / Q000235:genetics* / Q000528:radiation effects; D011038:Rothmund-Thomson Syndrome / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000235:genetics* / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins; D012689:Sequence Homology, Nucleic Acid; D012854:Sister Chromatid Exchange / Q000235:genetics / Q000528:radiation effects; D013172:Spores, Fungal / Q000166:cytology / Q000201:enzymology / Q000235:genetics / Q000528:radiation effects; D014466:Ultraviolet Rays; D014898:Werner Syndrome / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; C061376:SRS2 protein, S cerevisiae; C495151:RAD51 protein, S cerevisiae; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; C090472:SGS1 protein, S cerevisiae; D004265:DNA Helicases; D053484:RecQ Helicases