Suppression of spontaneous genome rearrangements in yeast DNA helicase mutants.
Saccharomyces cerevisiae mutants lacking two of the three DNA helicases Sgs1, Srs2, and Rrm3 exhibit slow growth that is suppressed by disrupting homologous recombination. Cells lacking Sgs1 and Rrm3 accumulate gross-chromosomal rearrangements (GCRs) that are suppressed by the DNA damage checkpoint and by homologous recombination-defective mutations. In contrast, rrm3, srs2, and srs2 rrm3 mutants have wild-type GCR rates. GCR types in helicase double mutants include telomere additions, translocations, and broken DNAs healed by a complex process of hairpin-mediated inversion. Spontaneous activation of the Rad53 checkpoint kinase in the rrm3 mutant depends on the Mec3/Rad24 DNA damage sensors and results from activation of the Mec1/Rad9-dependent DNA damage response rather than the Mrc1-dependent replication stress response. Moreover, helicase double mutants accumulate Rad51-dependent Ddc2 foci, indicating the presence of recombination intermediates that are sensed by checkpoints. These findings demonstrate that different nonreplicative helicases function at the interface between replication and repair to maintain genome integrity.
Schmidt
Kristina H
KH
Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA. kschmidt@cas.usf.edu
Kolodner
Richard D
RD
D048868:Adaptor Proteins, Signal Transducing; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D064447:Checkpoint Kinase 2; D015825:Chromosomes, Fungal / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D016681:Genome, Fungal / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C440014:LCD1 protein, S cerevisiae; C099938:MEC3 protein, S cerevisiae; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D004265:DNA Helicases