MRX (Mre11/Rad50/Xrs2) mutants reveal dual intra-S-phase checkpoint systems in budding yeast.
The intra-S-phase checkpoint is a signaling pathway that induces slow DNA replication in the presence of DNA damage. In humans, defects in this checkpoint pathway might account for phenotypes seen in autosomal recessive diseases including ataxia telangiectasia-like disorder and Nijmegen breakage syndrome, where MRN complex components,Mre11 and Nbs1, are mutated. Here we provide evidence that the equivalent budding yeast complex, MRX (Mre11/Rad50/Xrs2), is not required for the intra-S-phase checkpoint in response to DNA alkylation damage, but is required in the presence of double-stranded DNA breaks. These data indicate, at least in budding yeast, that alternate pathways enforce replication slowing depending on the particular DNA lesion.
Andrews
Catherine A
CA
Department of Genetics, Cell Biology & Development, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Clarke
Duncan J
DJ
D001761:Bleomycin / Q000494:pharmacology; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002469:Cell Separation; D064447:Checkpoint Kinase 2; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004271:DNA, Fungal; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000235:genetics* / Q000502:physiology*; D005090:Exodeoxyribonucleases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D005434:Flow Cytometry; D005720:Gamma Rays; D017353:Gene Deletion; D009154:Mutation; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D004718:Saccharomycetales; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C478035:Nbs1 protein, S pombe; C086930:RAD50 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C086929:XRS2 protein, S cerevisiae; D001761:Bleomycin; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae